Materiały źródłowe

• #1

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9263675/

  Vitiligo is a complex disease whose pathogenesis results from the interaction of genetic components, metabolic factors linked to cellular oxidative stress, melanocyte adhesion to the epithelium, and immunity (innate and adaptive), which culminate in aggression against melanocytes. […] In vitiligo, melanocytes are more sensitive to oxidative damage, leading to the increased expression of proinflammatory proteins such as HSP70. […] The lower expression of epithelial adhesion molecules, such as DDR1 and E-cadherin, facilitates damage to melanocytes and exposure of antigens that favor autoimmunity. […] Activation of the type 1-IFN pathway perpetuates the direct action of CD8+ cells against melanocytes, facilitated by regulatory T-cell dysfunction. […] The identification of several genes involved in these processes sets the stage for disease development and maintenance.

• #2 Update on the pathogenesis of vitiligo | Anais Brasileiros de Dermatologia (Portuguese)

  http://www.anaisdedermatologia.org.br/pt-update-on-pathogenesis-vitiligo-avance-S0365059622000654

  Vitiligo is a complex disease whose pathogenesis results from the interaction of genetic components, metabolic factors linked to cellular oxidative stress, melanocyte adhesion to the epithelium, and immunity (innate and adaptive), which culminate in aggression against melanocytes. […] In vitiligo, melanocytes are more sensitive to oxidative damage, leading to the increased expression of proinflammatory proteins such as HSP70. […] The lower expression of epithelial adhesion molecules, such as DDR1 and E-cadherin, facilitates damage to melanocytes and exposure of antigens that favor autoimmunity. […] Activation of the type 1-IFN pathway perpetuates the direct action of CD8+ cells against melanocytes, facilitated by regulatory T-cell dysfunction. […] The identification of several genes involved in these processes sets the stage for disease development and maintenance.

• #3 SciELO Brasil – Update on the pathogenesis of vitiligo Update on the pathogenesis of vitiligo

  https://www.scielo.br/j/abd/a/rGFjzRRxSLpMJ7y8Cxdz9HD/

  However, the relationship of vitiligo with environmental factors, psychological stress, comorbidities, and the elements that define individual susceptibility to the disease are a challenge to the integration of theories related to its pathogenesis. […] Its pathogenesis is multifactorial; however, the exact mechanisms that integrate the individual genetic susceptibility, melanocyte auto aggression, and failure of immune tolerance mechanisms are still not fully elucidated. […] HLA class I and II-related genes have been implicated in the pathogenesis of vitiligo. […] The oxidative stress that occurs in the melanocyte, as mentioned before, is possibly the autoimmunity trigger in vitiligo. […] The communication between the melanocyte and the innate immune system seems to occur through the secretion of exosomes, which contain melanocyte-specific antigens, miRNAs, heat shock proteins, and DAMPs (damage-associated molecular patterns).

• #4 Vitiligo, from Pathogenesis to Therapeutic Advances: State of the Art

  https://www.mdpi.com/1422-0067/24/5/4910

  Vitiligo is an acquired hypopigmentation of the skin due to a progressive selective loss of melanocytes; it has a prevalence of 1–2% and appears as rounded, well-demarcated white macules. The etiopathology of the disease has not been well defined, but multiple factors contribute to melanocyte loss: metabolic abnormalities, oxidative stress, inflammation, and autoimmunity. Therefore, a convergence theory was proposed that combines all existing theories into a comprehensive one in which several mechanisms contribute to the reduction of melanocyte viability. […] Although each of these pathogenetic hypotheses are still under discussion, there is now an agreement on the autoimmune and oxidative stress theories as leading processes in vitiligo pathogenesis. […] The precise etiology and pathophysiology are complex, and there is still much debate about the various theories on the loss of melanocyte function. Multiple pathophysiological mechanisms, including genetics, autoimmunity, oxidative stress, and neurological system dysfunction, have been proposed.

• #5 Vitiligo – Wikipedia

  https://en.wikipedia.org/wiki/Vitiligo

  A genome wide association study found approximately 36 independent susceptibility loci for generalized vitiligo. […] The TYR gene encodes the protein tyrosinase, which is not a component of the immune system but is an enzyme of the melanocyte that catalyzes melanin biosynthesis, and a major autoantigen in generalized vitiligo. […] Vitiligo is sometimes associated with autoimmune and inflammatory diseases such as Hashimoto’s thyroiditis, scleroderma, rheumatoid arthritis, type 1 diabetes mellitus, psoriasis, Addison’s disease, pernicious anemia, alopecia areata, systemic lupus erythematosus, and celiac disease. […] Numerous whole-exome sequencing studies have demonstrated that vitiligo is associated with polymorphisms in genes involved in the response to oxidative stress such as CAT, SOD1, SOD2, SOD3, NFE2L2, HMOX1, GST-M1 or GST-T1 supporting the association of elevated levels of reactive oxygen species in melanocytes with the induction of an auto-immune response.

• #6 Vitiligo – Wikipedia

  https://en.wikipedia.org/wiki/Vitiligo

  A genome wide association study found approximately 36 independent susceptibility loci for generalized vitiligo. […] The TYR gene encodes the protein tyrosinase, which is not a component of the immune system but is an enzyme of the melanocyte that catalyzes melanin biosynthesis, and a major autoantigen in generalized vitiligo. […] Vitiligo is sometimes associated with autoimmune and inflammatory diseases such as Hashimoto’s thyroiditis, scleroderma, rheumatoid arthritis, type 1 diabetes mellitus, psoriasis, Addison’s disease, pernicious anemia, alopecia areata, systemic lupus erythematosus, and celiac disease. […] Numerous whole-exome sequencing studies have demonstrated that vitiligo is associated with polymorphisms in genes involved in the response to oxidative stress such as CAT, SOD1, SOD2, SOD3, NFE2L2, HMOX1, GST-M1 or GST-T1 supporting the association of elevated levels of reactive oxygen species in melanocytes with the induction of an auto-immune response.

• #7 Update on the pathogenesis of vitiligo | Anais Brasileiros de Dermatologia (Portuguese)

  http://www.anaisdedermatologia.org.br/pt-update-on-pathogenesis-vitiligo-avance-S0365059622000654

  Its pathogenesis is multifactorial; however, the exact mechanisms that integrate the individual genetic susceptibility, melanocyte auto aggression, and failure of immune tolerance mechanisms are still not fully elucidated. […] The mapping of genetic risk factors for vitiligo was performed by linkage analysis followed by positional cloning. […] Linkage analysis assesses the nonrandom segregation of chromosomal regions among affected individuals in families with vitiligo. […] Seven loci have been linked to vitiligo susceptibility, of which four were observed in European populations and three in Chinese populations. […] Chromosome 22q12 has been associated with the pathogenesis of vitiligo, with the variants that regulate XBP1 gene expression being the risk factor indicated in the 22q12 region.

• #8 Update on the pathogenesis of vitiligo | Anais Brasileiros de Dermatologia (Portuguese)

  http://www.anaisdedermatologia.org.br/pt-update-on-pathogenesis-vitiligo-avance-S0365059622000654

  Its pathogenesis is multifactorial; however, the exact mechanisms that integrate the individual genetic susceptibility, melanocyte auto aggression, and failure of immune tolerance mechanisms are still not fully elucidated. […] The mapping of genetic risk factors for vitiligo was performed by linkage analysis followed by positional cloning. […] Linkage analysis assesses the nonrandom segregation of chromosomal regions among affected individuals in families with vitiligo. […] Seven loci have been linked to vitiligo susceptibility, of which four were observed in European populations and three in Chinese populations. […] Chromosome 22q12 has been associated with the pathogenesis of vitiligo, with the variants that regulate XBP1 gene expression being the risk factor indicated in the 22q12 region.

• #9 Vitiligo, from Pathogenesis to Therapeutic Advances: State of the Art

  https://www.mdpi.com/1422-0067/24/5/4910

  Genetic studies confirm the autoimmune hypothesis as the vitiligo leading pathogenetic mechanism, since around 85% of the vitiligo susceptibility genes encode molecules implicated in innate and adaptive immunity and apoptosis. […] Indeed, innate immune cells seem to be early activated by endogenous and exogenous stress signals released from melanocytes and keratinocytes, leading to the subsequent activation of an adaptive immune response, both humoral and cell-mediated, causing the targeted autoimmune destruction of melanocytes. […] Oxidative stress plays a crucial role in initiating vitiligo with melanocyte destruction. […] Melanocytes seem to be both the instigators and the victims of oxidative stress. Melanocytes from patients with vitiligo are more susceptible to oxidative stress than those from controls without vitiligo.

• #10 SciELO Brasil – Update on the pathogenesis of vitiligo Update on the pathogenesis of vitiligo

  https://www.scielo.br/j/abd/a/rGFjzRRxSLpMJ7y8Cxdz9HD/

  However, the relationship of vitiligo with environmental factors, psychological stress, comorbidities, and the elements that define individual susceptibility to the disease are a challenge to the integration of theories related to its pathogenesis. […] Its pathogenesis is multifactorial; however, the exact mechanisms that integrate the individual genetic susceptibility, melanocyte auto aggression, and failure of immune tolerance mechanisms are still not fully elucidated. […] HLA class I and II-related genes have been implicated in the pathogenesis of vitiligo. […] The oxidative stress that occurs in the melanocyte, as mentioned before, is possibly the autoimmunity trigger in vitiligo. […] The communication between the melanocyte and the innate immune system seems to occur through the secretion of exosomes, which contain melanocyte-specific antigens, miRNAs, heat shock proteins, and DAMPs (damage-associated molecular patterns).

• #11 Update on the pathogenesis of vitiligo | Anais Brasileiros de Dermatologia (Portuguese)

  http://www.anaisdedermatologia.org.br/pt-update-on-pathogenesis-vitiligo-avance-S0365059622000654

  HLA class I and II-related genes have been implicated in the pathogenesis of vitiligo. […] The oxidative stress that occurs in the melanocyte, as mentioned before, is possibly the autoimmunity trigger in vitiligo. […] The communication between the melanocyte and the innate immune system seems to occur through the secretion of exosomes, which contain melanocyte-specific antigens, miRNAs, heat shock proteins, and DAMPs (damage-associated molecular patterns). […] The DAMP with the highest evidence of association with vitiligo to date is HSP70 (heat shock protein 70). […] Cytotoxic CD8+ T-cells are necessary and sufficient for the destruction of melanocytes, acting as an effector arm of autoimmunity. […] The lesions are caused by effector CD8+ T-lymphocytes in the initial or active phase of the disease and by recirculating and resident memory CD8+T (TEM) lymphocytes in the stable phase.

• #12 Vitiligo, from Pathogenesis to Therapeutic Advances: State of the Art

  https://www.mdpi.com/1422-0067/24/5/4910

  Genetic studies confirm the autoimmune hypothesis as the vitiligo leading pathogenetic mechanism, since around 85% of the vitiligo susceptibility genes encode molecules implicated in innate and adaptive immunity and apoptosis. […] Indeed, innate immune cells seem to be early activated by endogenous and exogenous stress signals released from melanocytes and keratinocytes, leading to the subsequent activation of an adaptive immune response, both humoral and cell-mediated, causing the targeted autoimmune destruction of melanocytes. […] Oxidative stress plays a crucial role in initiating vitiligo with melanocyte destruction. […] Melanocytes seem to be both the instigators and the victims of oxidative stress. Melanocytes from patients with vitiligo are more susceptible to oxidative stress than those from controls without vitiligo.

• #13

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9263675/

  Melanocytes cultured from unaffected areas in patients with vitiligo have a greater susceptibility to oxidative stress than from controls without vitiligo, demonstrating an overall susceptibility of the patient with vitiligo to oxidative damage. […] The oxidative stress that occurs in the melanocyte, as mentioned before, is possibly the autoimmunity trigger in vitiligo. […] The communication between the melanocyte and the innate immune system seems to occur through the secretion of exosomes, which contain melanocyte-specific antigens, miRNAs, heat shock proteins, and DAMPs (damage-associated molecular patterns). […] The DAMP with the highest evidence of association with vitiligo to date is HSP70 (heat shock protein 70). […] The induced HSP70 is present in lesional and perilesional skin in vitiligo.

• #14 Vitiligo, from Pathogenesis to Therapeutic Advances: State of the Art

  https://www.mdpi.com/1422-0067/24/5/4910

  Genetic studies confirm the autoimmune hypothesis as the vitiligo leading pathogenetic mechanism, since around 85% of the vitiligo susceptibility genes encode molecules implicated in innate and adaptive immunity and apoptosis. […] Indeed, innate immune cells seem to be early activated by endogenous and exogenous stress signals released from melanocytes and keratinocytes, leading to the subsequent activation of an adaptive immune response, both humoral and cell-mediated, causing the targeted autoimmune destruction of melanocytes. […] Oxidative stress plays a crucial role in initiating vitiligo with melanocyte destruction. […] Melanocytes seem to be both the instigators and the victims of oxidative stress. Melanocytes from patients with vitiligo are more susceptible to oxidative stress than those from controls without vitiligo.

• #15

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9263675/

  However, the relationship of vitiligo with environmental factors, psychological stress, comorbidities, and the elements that define individual susceptibility to the disease are a challenge to the integration of theories related to its pathogenesis. […] Its pathogenesis is multifactorial; however, the exact mechanisms that integrate the individual genetic susceptibility, melanocyte auto aggression, and failure of immune tolerance mechanisms are still not fully elucidated. […] Autoimmunity, melanocyte adhesion, and metabolic dysfunction have been suggested as contributing to the etiology of vitiligo, and several genes based on the above mechanisms have been tested. […] The accumulation of reactive oxygen species in the epidermis can inhibit the BCHE enzymatic activity. […] The theory of vitiligo development due to oxidative stress (OS) suggests that ROS production would be induced by multiple intrinsic factors (such as inflammation and protein synthesis), as well as extrinsic ones, such as exposure to ultraviolet radiation pollutants, and phenolic compounds.

• #16

  https://www.jci.org/articles/view/185785

  Melanocyte biology. Early studies of melanocytes from patients with vitiligo revealed that they were abnormal when compared with those from healthy individuals. They were more difficult to culture and demonstrated elevated levels of cellular stress, including activation of the unfolded protein response and presence of reactive oxygen species. Furthermore, certain chemical exposures were found to induce and exacerbate vitiligo in patients, such as the presence of monobenzone in gloves used by factory workers in the early 1900s and more recently the use of permanent hair dyes or skin-lightening cosmetics. These chemicals, most of which are phenols, resemble the structure of the amino acid tyrosine, a building block of melanin, and thus interfere with the energy-demanding process of melanogenesis, resulting in increased cellular stress and release of damage-associated molecular patterns such as heat shock proteins like HSP70 that activate cytokine release and inflammation. This likely leads to activation of innate immunity and ultimately adaptive responses that target melanocytes for destruction. These examples highlight the fact that melanocytes are not simply bystanders in vitiligo progression, but play an active role in their own destruction. Parallel observations about target cell stress have been made in other autoimmune diseases, such as T1D, multiple sclerosis (MS), and autoimmune thyroiditis.

• #17

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9263675/

  Melanocytes cultured from unaffected areas in patients with vitiligo have a greater susceptibility to oxidative stress than from controls without vitiligo, demonstrating an overall susceptibility of the patient with vitiligo to oxidative damage. […] The oxidative stress that occurs in the melanocyte, as mentioned before, is possibly the autoimmunity trigger in vitiligo. […] The communication between the melanocyte and the innate immune system seems to occur through the secretion of exosomes, which contain melanocyte-specific antigens, miRNAs, heat shock proteins, and DAMPs (damage-associated molecular patterns). […] The DAMP with the highest evidence of association with vitiligo to date is HSP70 (heat shock protein 70). […] The induced HSP70 is present in lesional and perilesional skin in vitiligo.

• #18 SciELO Brasil – Update on the pathogenesis of vitiligo Update on the pathogenesis of vitiligo

  https://www.scielo.br/j/abd/a/rGFjzRRxSLpMJ7y8Cxdz9HD/

  However, the relationship of vitiligo with environmental factors, psychological stress, comorbidities, and the elements that define individual susceptibility to the disease are a challenge to the integration of theories related to its pathogenesis. […] Its pathogenesis is multifactorial; however, the exact mechanisms that integrate the individual genetic susceptibility, melanocyte auto aggression, and failure of immune tolerance mechanisms are still not fully elucidated. […] HLA class I and II-related genes have been implicated in the pathogenesis of vitiligo. […] The oxidative stress that occurs in the melanocyte, as mentioned before, is possibly the autoimmunity trigger in vitiligo. […] The communication between the melanocyte and the innate immune system seems to occur through the secretion of exosomes, which contain melanocyte-specific antigens, miRNAs, heat shock proteins, and DAMPs (damage-associated molecular patterns).

• #19 Update on the pathogenesis of vitiligo | Anais Brasileiros de Dermatologia

  https://www.anaisdedermatologia.org.br/en-update-on-pathogenesis-vitiligo-articulo-S0365059622000654

  However, the relationship of vitiligo with environmental factors, psychological stress, comorbidities, and the elements that define individual susceptibility to the disease are a challenge to the integration of theories related to its pathogenesis. […] Its pathogenesis is multifactorial; however, the exact mechanisms that integrate the individual genetic susceptibility, melanocyte auto aggression, and failure of immune tolerance mechanisms are still not fully elucidated. […] The oxidative stress that occurs in the melanocyte, as mentioned before, is possibly the autoimmunity trigger in vitiligo. […] The communication between the melanocyte and the innate immune system seems to occur through the secretion of exosomes, which contain melanocyte-specific antigens, miRNAs, heat shock proteins, and DAMPs (damage-associated molecular patterns).

• #20

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9263675/

  However, the relationship of vitiligo with environmental factors, psychological stress, comorbidities, and the elements that define individual susceptibility to the disease are a challenge to the integration of theories related to its pathogenesis. […] Its pathogenesis is multifactorial; however, the exact mechanisms that integrate the individual genetic susceptibility, melanocyte auto aggression, and failure of immune tolerance mechanisms are still not fully elucidated. […] Autoimmunity, melanocyte adhesion, and metabolic dysfunction have been suggested as contributing to the etiology of vitiligo, and several genes based on the above mechanisms have been tested. […] The accumulation of reactive oxygen species in the epidermis can inhibit the BCHE enzymatic activity. […] The theory of vitiligo development due to oxidative stress (OS) suggests that ROS production would be induced by multiple intrinsic factors (such as inflammation and protein synthesis), as well as extrinsic ones, such as exposure to ultraviolet radiation pollutants, and phenolic compounds.

• #21 :: AD :: Annals of Dermatology

  https://anndermatol.org/DOIx.php?id=10.5021/ad.23.065

  Increased oxidative stress not only damages melanocytes, but also induces autoimmunity through the upregulation of the calreticulin expression and translocation to the cell membrane. […] These findings indicate that skin resident cells including keratinocytes and dermal fibroblasts may play a key role in regulating the microenvironment of vitiligo immunity. […] Correctly understanding the mechanisms for ROS accumulation and the associated types of unique autoimmunity is expected to lead to the proper clinical management of vitiligo. […] Recent studies have shown that the local immune environment generated by vitiligo lesions plays an important role in the onset and maintenance of vitiligo. […] IFN–signals activate the intracellular JAK-signal transducer and activator (STAT) 1 pathway to produce CXCL9/10 in keratinocytes, after which cytotoxic T cells expressing the receptor CXCR3 migrate to the epidermis and release molecules, such as granzyme B and perforin, to attack melanocytes. […] Furthermore, the mechanism by which IFN- reactivates keratinocytes has been clarified; therefore, JAK-targeted therapeutic applications have come to be used for the pathology of the IFN–JAK-STAT1 axis.

• #22

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9263675/

  Melanocytes cultured from unaffected areas in patients with vitiligo have a greater susceptibility to oxidative stress than from controls without vitiligo, demonstrating an overall susceptibility of the patient with vitiligo to oxidative damage. […] The oxidative stress that occurs in the melanocyte, as mentioned before, is possibly the autoimmunity trigger in vitiligo. […] The communication between the melanocyte and the innate immune system seems to occur through the secretion of exosomes, which contain melanocyte-specific antigens, miRNAs, heat shock proteins, and DAMPs (damage-associated molecular patterns). […] The DAMP with the highest evidence of association with vitiligo to date is HSP70 (heat shock protein 70). […] The induced HSP70 is present in lesional and perilesional skin in vitiligo.

• #23 SciELO Brasil – Update on the pathogenesis of vitiligo Update on the pathogenesis of vitiligo

  https://www.scielo.br/j/abd/a/rGFjzRRxSLpMJ7y8Cxdz9HD/

  However, the relationship of vitiligo with environmental factors, psychological stress, comorbidities, and the elements that define individual susceptibility to the disease are a challenge to the integration of theories related to its pathogenesis. […] Its pathogenesis is multifactorial; however, the exact mechanisms that integrate the individual genetic susceptibility, melanocyte auto aggression, and failure of immune tolerance mechanisms are still not fully elucidated. […] HLA class I and II-related genes have been implicated in the pathogenesis of vitiligo. […] The oxidative stress that occurs in the melanocyte, as mentioned before, is possibly the autoimmunity trigger in vitiligo. […] The communication between the melanocyte and the innate immune system seems to occur through the secretion of exosomes, which contain melanocyte-specific antigens, miRNAs, heat shock proteins, and DAMPs (damage-associated molecular patterns).

• #24 Update on the pathogenesis of vitiligo | Anais Brasileiros de Dermatologia

  https://www.anaisdedermatologia.org.br/en-update-on-pathogenesis-vitiligo-articulo-S0365059622000654

  However, the relationship of vitiligo with environmental factors, psychological stress, comorbidities, and the elements that define individual susceptibility to the disease are a challenge to the integration of theories related to its pathogenesis. […] Its pathogenesis is multifactorial; however, the exact mechanisms that integrate the individual genetic susceptibility, melanocyte auto aggression, and failure of immune tolerance mechanisms are still not fully elucidated. […] The oxidative stress that occurs in the melanocyte, as mentioned before, is possibly the autoimmunity trigger in vitiligo. […] The communication between the melanocyte and the innate immune system seems to occur through the secretion of exosomes, which contain melanocyte-specific antigens, miRNAs, heat shock proteins, and DAMPs (damage-associated molecular patterns).

• #25

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9263675/

  Melanocytes cultured from unaffected areas in patients with vitiligo have a greater susceptibility to oxidative stress than from controls without vitiligo, demonstrating an overall susceptibility of the patient with vitiligo to oxidative damage. […] The oxidative stress that occurs in the melanocyte, as mentioned before, is possibly the autoimmunity trigger in vitiligo. […] The communication between the melanocyte and the innate immune system seems to occur through the secretion of exosomes, which contain melanocyte-specific antigens, miRNAs, heat shock proteins, and DAMPs (damage-associated molecular patterns). […] The DAMP with the highest evidence of association with vitiligo to date is HSP70 (heat shock protein 70). […] The induced HSP70 is present in lesional and perilesional skin in vitiligo.

• #26 SciELO Brasil – Update on the pathogenesis of vitiligo Update on the pathogenesis of vitiligo

  https://www.scielo.br/j/abd/a/rGFjzRRxSLpMJ7y8Cxdz9HD/

  The DAMP with the highest evidence of association with vitiligo to date is HSP70 (heat shock protein 70). […] The induced HSP70 is present in lesional and perilesional skin in vitiligo. […] The activation of innate immunity triggered by damage to melanocytes affected by oxidative stress promotes cytokine secretion and antigen presentation, resulting in the adaptive immune system activation, in which autoreactive T-cells amplify damage to melanocytes in vitiligo-affected skin. […] Cytotoxic CD8+ T-cells are necessary and sufficient for the destruction of melanocytes, acting as an effector arm of autoimmunity. […] The lesions are caused by effector CD8+ T-lymphocytes in the initial or active phase of the disease and by recirculating and resident memory CD8 + T (TEM) lymphocytes in the stable phase.

• #27 Update on the pathogenesis of vitiligo | Anais Brasileiros de Dermatologia

  https://www.anaisdedermatologia.org.br/en-update-on-pathogenesis-vitiligo-articulo-S0365059622000654

  The DAMP with the highest evidence of association with vitiligo to date is HSP70 (heat shock protein 70). […] The induced HSP70 is present in lesional and perilesional skin in vitiligo. […] The activation of innate immunity triggered by damage to melanocytes affected by oxidative stress promotes cytokine secretion and antigen presentation, resulting in the adaptive immune system activation, in which autoreactive T-cells amplify damage to melanocytes in vitiligo-affected skin. […] Cytotoxic T-lymphocytes (CD8+) are the main cells implicated in disease pathogenesis. […] The type I IFN pathway is a key point for the start of the vitiligo immune response. […] Cytotoxic CD8+ T-cells are necessary and sufficient for the destruction of melanocytes, acting as an effector arm of autoimmunity.

• #28

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9263675/

  Melanocytes cultured from unaffected areas in patients with vitiligo have a greater susceptibility to oxidative stress than from controls without vitiligo, demonstrating an overall susceptibility of the patient with vitiligo to oxidative damage. […] The oxidative stress that occurs in the melanocyte, as mentioned before, is possibly the autoimmunity trigger in vitiligo. […] The communication between the melanocyte and the innate immune system seems to occur through the secretion of exosomes, which contain melanocyte-specific antigens, miRNAs, heat shock proteins, and DAMPs (damage-associated molecular patterns). […] The DAMP with the highest evidence of association with vitiligo to date is HSP70 (heat shock protein 70). […] The induced HSP70 is present in lesional and perilesional skin in vitiligo.

• #29 SciELO Brasil – Update on the pathogenesis of vitiligo Update on the pathogenesis of vitiligo

  https://www.scielo.br/j/abd/a/rGFjzRRxSLpMJ7y8Cxdz9HD/

  The DAMP with the highest evidence of association with vitiligo to date is HSP70 (heat shock protein 70). […] The induced HSP70 is present in lesional and perilesional skin in vitiligo. […] The activation of innate immunity triggered by damage to melanocytes affected by oxidative stress promotes cytokine secretion and antigen presentation, resulting in the adaptive immune system activation, in which autoreactive T-cells amplify damage to melanocytes in vitiligo-affected skin. […] Cytotoxic CD8+ T-cells are necessary and sufficient for the destruction of melanocytes, acting as an effector arm of autoimmunity. […] The lesions are caused by effector CD8+ T-lymphocytes in the initial or active phase of the disease and by recirculating and resident memory CD8 + T (TEM) lymphocytes in the stable phase.

• #30 Update on the pathogenesis of vitiligo | Anais Brasileiros de Dermatologia

  https://www.anaisdedermatologia.org.br/en-update-on-pathogenesis-vitiligo-articulo-S0365059622000654

  The DAMP with the highest evidence of association with vitiligo to date is HSP70 (heat shock protein 70). […] The induced HSP70 is present in lesional and perilesional skin in vitiligo. […] The activation of innate immunity triggered by damage to melanocytes affected by oxidative stress promotes cytokine secretion and antigen presentation, resulting in the adaptive immune system activation, in which autoreactive T-cells amplify damage to melanocytes in vitiligo-affected skin. […] Cytotoxic T-lymphocytes (CD8+) are the main cells implicated in disease pathogenesis. […] The type I IFN pathway is a key point for the start of the vitiligo immune response. […] Cytotoxic CD8+ T-cells are necessary and sufficient for the destruction of melanocytes, acting as an effector arm of autoimmunity.

• #31

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9263675/

  The activation of innate immunity triggered by damage to melanocytes affected by oxidative stress promotes cytokine secretion and antigen presentation, resulting in the adaptive immune system activation, in which autoreactive T-cells amplify damage to melanocytes in vitiligo-affected skin. […] Cytotoxic T-lymphocytes (CD8+) are the main cells implicated in disease pathogenesis. […] The type I IFN pathway is a key point for the start of the vitiligo immune response. […] The lesions are caused by effector CD8+ T-lymphocytes in the initial or active phase of the disease and by recirculating and resident memory CD8+T (TEM) lymphocytes in the stable phase. […] The mechanism of aggression is based on the production of inflammatory cytokines such as TNF and IFN, in addition to the release of granzymes and perforins, which cause direct damage to melanocytes.

• #32 SciELO Brasil – Update on the pathogenesis of vitiligo Update on the pathogenesis of vitiligo

  https://www.scielo.br/j/abd/a/rGFjzRRxSLpMJ7y8Cxdz9HD/

  The DAMP with the highest evidence of association with vitiligo to date is HSP70 (heat shock protein 70). […] The induced HSP70 is present in lesional and perilesional skin in vitiligo. […] The activation of innate immunity triggered by damage to melanocytes affected by oxidative stress promotes cytokine secretion and antigen presentation, resulting in the adaptive immune system activation, in which autoreactive T-cells amplify damage to melanocytes in vitiligo-affected skin. […] Cytotoxic CD8+ T-cells are necessary and sufficient for the destruction of melanocytes, acting as an effector arm of autoimmunity. […] The lesions are caused by effector CD8+ T-lymphocytes in the initial or active phase of the disease and by recirculating and resident memory CD8 + T (TEM) lymphocytes in the stable phase.

• #33 Update on the pathogenesis of vitiligo | Anais Brasileiros de Dermatologia

  https://www.anaisdedermatologia.org.br/en-update-on-pathogenesis-vitiligo-articulo-S0365059622000654

  The DAMP with the highest evidence of association with vitiligo to date is HSP70 (heat shock protein 70). […] The induced HSP70 is present in lesional and perilesional skin in vitiligo. […] The activation of innate immunity triggered by damage to melanocytes affected by oxidative stress promotes cytokine secretion and antigen presentation, resulting in the adaptive immune system activation, in which autoreactive T-cells amplify damage to melanocytes in vitiligo-affected skin. […] Cytotoxic T-lymphocytes (CD8+) are the main cells implicated in disease pathogenesis. […] The type I IFN pathway is a key point for the start of the vitiligo immune response. […] Cytotoxic CD8+ T-cells are necessary and sufficient for the destruction of melanocytes, acting as an effector arm of autoimmunity.

• #34

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9263675/

  The activation of innate immunity triggered by damage to melanocytes affected by oxidative stress promotes cytokine secretion and antigen presentation, resulting in the adaptive immune system activation, in which autoreactive T-cells amplify damage to melanocytes in vitiligo-affected skin. […] Cytotoxic T-lymphocytes (CD8+) are the main cells implicated in disease pathogenesis. […] The type I IFN pathway is a key point for the start of the vitiligo immune response. […] The lesions are caused by effector CD8+ T-lymphocytes in the initial or active phase of the disease and by recirculating and resident memory CD8+T (TEM) lymphocytes in the stable phase. […] The mechanism of aggression is based on the production of inflammatory cytokines such as TNF and IFN, in addition to the release of granzymes and perforins, which cause direct damage to melanocytes.

• #35 SciELO Brasil – Update on the pathogenesis of vitiligo Update on the pathogenesis of vitiligo

  https://www.scielo.br/j/abd/a/rGFjzRRxSLpMJ7y8Cxdz9HD/

  The DAMP with the highest evidence of association with vitiligo to date is HSP70 (heat shock protein 70). […] The induced HSP70 is present in lesional and perilesional skin in vitiligo. […] The activation of innate immunity triggered by damage to melanocytes affected by oxidative stress promotes cytokine secretion and antigen presentation, resulting in the adaptive immune system activation, in which autoreactive T-cells amplify damage to melanocytes in vitiligo-affected skin. […] Cytotoxic CD8+ T-cells are necessary and sufficient for the destruction of melanocytes, acting as an effector arm of autoimmunity. […] The lesions are caused by effector CD8+ T-lymphocytes in the initial or active phase of the disease and by recirculating and resident memory CD8 + T (TEM) lymphocytes in the stable phase.

• #36 Update on the pathogenesis of vitiligo | Anais Brasileiros de Dermatologia

  https://www.anaisdedermatologia.org.br/en-update-on-pathogenesis-vitiligo-articulo-S0365059622000654

  The DAMP with the highest evidence of association with vitiligo to date is HSP70 (heat shock protein 70). […] The induced HSP70 is present in lesional and perilesional skin in vitiligo. […] The activation of innate immunity triggered by damage to melanocytes affected by oxidative stress promotes cytokine secretion and antigen presentation, resulting in the adaptive immune system activation, in which autoreactive T-cells amplify damage to melanocytes in vitiligo-affected skin. […] Cytotoxic T-lymphocytes (CD8+) are the main cells implicated in disease pathogenesis. […] The type I IFN pathway is a key point for the start of the vitiligo immune response. […] Cytotoxic CD8+ T-cells are necessary and sufficient for the destruction of melanocytes, acting as an effector arm of autoimmunity.

• #37 SciELO Brasil – Update on the pathogenesis of vitiligo Update on the pathogenesis of vitiligo

  https://www.scielo.br/j/abd/a/rGFjzRRxSLpMJ7y8Cxdz9HD/

  The DAMP with the highest evidence of association with vitiligo to date is HSP70 (heat shock protein 70). […] The induced HSP70 is present in lesional and perilesional skin in vitiligo. […] The activation of innate immunity triggered by damage to melanocytes affected by oxidative stress promotes cytokine secretion and antigen presentation, resulting in the adaptive immune system activation, in which autoreactive T-cells amplify damage to melanocytes in vitiligo-affected skin. […] Cytotoxic CD8+ T-cells are necessary and sufficient for the destruction of melanocytes, acting as an effector arm of autoimmunity. […] The lesions are caused by effector CD8+ T-lymphocytes in the initial or active phase of the disease and by recirculating and resident memory CD8 + T (TEM) lymphocytes in the stable phase.

• #38 Update on the pathogenesis of vitiligo | Anais Brasileiros de Dermatologia

  https://www.anaisdedermatologia.org.br/en-update-on-pathogenesis-vitiligo-articulo-S0365059622000654

  The DAMP with the highest evidence of association with vitiligo to date is HSP70 (heat shock protein 70). […] The induced HSP70 is present in lesional and perilesional skin in vitiligo. […] The activation of innate immunity triggered by damage to melanocytes affected by oxidative stress promotes cytokine secretion and antigen presentation, resulting in the adaptive immune system activation, in which autoreactive T-cells amplify damage to melanocytes in vitiligo-affected skin. […] Cytotoxic T-lymphocytes (CD8+) are the main cells implicated in disease pathogenesis. […] The type I IFN pathway is a key point for the start of the vitiligo immune response. […] Cytotoxic CD8+ T-cells are necessary and sufficient for the destruction of melanocytes, acting as an effector arm of autoimmunity.

• #39

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9263675/

  The activation of innate immunity triggered by damage to melanocytes affected by oxidative stress promotes cytokine secretion and antigen presentation, resulting in the adaptive immune system activation, in which autoreactive T-cells amplify damage to melanocytes in vitiligo-affected skin. […] Cytotoxic T-lymphocytes (CD8+) are the main cells implicated in disease pathogenesis. […] The type I IFN pathway is a key point for the start of the vitiligo immune response. […] The lesions are caused by effector CD8+ T-lymphocytes in the initial or active phase of the disease and by recirculating and resident memory CD8+T (TEM) lymphocytes in the stable phase. […] The mechanism of aggression is based on the production of inflammatory cytokines such as TNF and IFN, in addition to the release of granzymes and perforins, which cause direct damage to melanocytes.

• #40 SciELO Brasil – Update on the pathogenesis of vitiligo Update on the pathogenesis of vitiligo

  https://www.scielo.br/j/abd/a/rGFjzRRxSLpMJ7y8Cxdz9HD/

  The DAMP with the highest evidence of association with vitiligo to date is HSP70 (heat shock protein 70). […] The induced HSP70 is present in lesional and perilesional skin in vitiligo. […] The activation of innate immunity triggered by damage to melanocytes affected by oxidative stress promotes cytokine secretion and antigen presentation, resulting in the adaptive immune system activation, in which autoreactive T-cells amplify damage to melanocytes in vitiligo-affected skin. […] Cytotoxic CD8+ T-cells are necessary and sufficient for the destruction of melanocytes, acting as an effector arm of autoimmunity. […] The lesions are caused by effector CD8+ T-lymphocytes in the initial or active phase of the disease and by recirculating and resident memory CD8 + T (TEM) lymphocytes in the stable phase.

• #41 Update on the pathogenesis of vitiligo | Anais Brasileiros de Dermatologia

  https://www.anaisdedermatologia.org.br/en-update-on-pathogenesis-vitiligo-articulo-S0365059622000654

  The lesions are caused by effector CD8+ T-lymphocytes in the initial or active phase of the disease and by recirculating and resident memory CD8+T (TEM) lymphocytes in the stable phase. […] The mechanism of aggression is based on the production of inflammatory cytokines such as TNF and IFN, in addition to the release of granzymes and perforins, which cause direct damage to melanocytes. […] The Janus kinase/signal transducers and transcription activators (JAK/STAT) pathway participate in the immunopathogenesis of vitiligo through its interaction with IFN. […] The exact mechanism by which topical therapies with corticosteroids and calcineurin inhibitors affect the disease pathogenesis has yet to be fully elucidated, but it is believed that they reduce the lymphocytic infiltrate and TNF expression.

• #42

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9263675/

  The activation of innate immunity triggered by damage to melanocytes affected by oxidative stress promotes cytokine secretion and antigen presentation, resulting in the adaptive immune system activation, in which autoreactive T-cells amplify damage to melanocytes in vitiligo-affected skin. […] Cytotoxic T-lymphocytes (CD8+) are the main cells implicated in disease pathogenesis. […] The type I IFN pathway is a key point for the start of the vitiligo immune response. […] The lesions are caused by effector CD8+ T-lymphocytes in the initial or active phase of the disease and by recirculating and resident memory CD8+T (TEM) lymphocytes in the stable phase. […] The mechanism of aggression is based on the production of inflammatory cytokines such as TNF and IFN, in addition to the release of granzymes and perforins, which cause direct damage to melanocytes.

• #43 Update on the pathogenesis of vitiligo | Anais Brasileiros de Dermatologia

  https://www.anaisdedermatologia.org.br/en-update-on-pathogenesis-vitiligo-articulo-S0365059622000654

  The lesions are caused by effector CD8+ T-lymphocytes in the initial or active phase of the disease and by recirculating and resident memory CD8+T (TEM) lymphocytes in the stable phase. […] The mechanism of aggression is based on the production of inflammatory cytokines such as TNF and IFN, in addition to the release of granzymes and perforins, which cause direct damage to melanocytes. […] The Janus kinase/signal transducers and transcription activators (JAK/STAT) pathway participate in the immunopathogenesis of vitiligo through its interaction with IFN. […] The exact mechanism by which topical therapies with corticosteroids and calcineurin inhibitors affect the disease pathogenesis has yet to be fully elucidated, but it is believed that they reduce the lymphocytic infiltrate and TNF expression.

• #44

  https://journals.lww.com/jdpa/fulltext/2025/01910/understanding_the_mechanism_of_disease_of_vitiligo.7.aspx

  During vitiligo progression, a subset of the CD8+ T cells in the skin transform into skin resident memory T cells. […] The activity and survival of skin resident memory T cells is maintained by interleukin-15 (IL-15), a cytokine that utilizes the JAK-STAT signaling pathway. […] Resident memory CD8+ T cells remain in the skin indefinitely, causing persistent depigmentation as well as disease relapse after treatment discontinuation. […] Blocking crucial steps of the disease process, such as IFN- or IL-15 signaling, may halt skin depigmentation and allow new melanocytes to migrate into depigmented lesions, leading to gradual repigmentation over time. […] Repigmentation often initiates from hair follicles, which serve as a reservoir for stem cells that differentiate into melanoblasts and give rise to new melanocytes.

• #45

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9263675/

  The activation of innate immunity triggered by damage to melanocytes affected by oxidative stress promotes cytokine secretion and antigen presentation, resulting in the adaptive immune system activation, in which autoreactive T-cells amplify damage to melanocytes in vitiligo-affected skin. […] Cytotoxic T-lymphocytes (CD8+) are the main cells implicated in disease pathogenesis. […] The type I IFN pathway is a key point for the start of the vitiligo immune response. […] The lesions are caused by effector CD8+ T-lymphocytes in the initial or active phase of the disease and by recirculating and resident memory CD8+T (TEM) lymphocytes in the stable phase. […] The mechanism of aggression is based on the production of inflammatory cytokines such as TNF and IFN, in addition to the release of granzymes and perforins, which cause direct damage to melanocytes.

• #46 SciELO Brasil – Update on the pathogenesis of vitiligo Update on the pathogenesis of vitiligo

  https://www.scielo.br/j/abd/a/rGFjzRRxSLpMJ7y8Cxdz9HD/

  The type I IFN pathway is a key point for the start of the vitiligo immune response. […] The Janus kinase/signal transducers and transcription activators (JAK/STAT) pathway participate in the immunopathogenesis of vitiligo through its interaction with IFN. […] In conclusion, the pathogenesis of vitiligo results from an interaction of elements (multifactorial), which suggests a genetic susceptibility basis, affected by environmental factors, oxidative stress, psychological factors, and patterns of autoimmune response.

• #47 Update on the pathogenesis of vitiligo | Anais Brasileiros de Dermatologia

  https://www.anaisdedermatologia.org.br/en-update-on-pathogenesis-vitiligo-articulo-S0365059622000654

  The lesions are caused by effector CD8+ T-lymphocytes in the initial or active phase of the disease and by recirculating and resident memory CD8+T (TEM) lymphocytes in the stable phase. […] The mechanism of aggression is based on the production of inflammatory cytokines such as TNF and IFN, in addition to the release of granzymes and perforins, which cause direct damage to melanocytes. […] The Janus kinase/signal transducers and transcription activators (JAK/STAT) pathway participate in the immunopathogenesis of vitiligo through its interaction with IFN. […] The exact mechanism by which topical therapies with corticosteroids and calcineurin inhibitors affect the disease pathogenesis has yet to be fully elucidated, but it is believed that they reduce the lymphocytic infiltrate and TNF expression.

• #48

  https://link.springer.com/article/10.1007/s13555-020-00447-y

  Several data link vitiligo to a type I IFN signature. […] The binding of IFN- to its receptor induces the Janus kinase/signal transducer and activator of the transcription (JAK/STAT) pathway, in particular JAK1-2 and STAT1 activation. […] Recent studies in vitiligo have demonstrated that IFN- induces the production of the CXCR3 ligands CXCL9 and CXCL10 by keratinocytes, thereby amplifying inflammation and the recruitment of immune cells expressing CXCR3 that will further promote vitiligo progression. […] Cytokines are key mediators of melanocyte loss in vitiligo and participate at every step of the pathogenesis of this disease. […] JAK inhibitors are showing promising results, but their broader effects can not reveal which predominant pathways are fully involved in the disease, supporting the notion that an intricate combination of multiple immune pathways are involved in the initiation and progression of the disease.

• #49

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9263675/

  The Janus kinase/signal transducers and transcription activators (JAK/STAT) pathway participate in the immunopathogenesis of vitiligo through its interaction with IFN. […] The exact mechanism by which topical therapies with corticosteroids and calcineurin inhibitors affect the disease pathogenesis has yet to be fully elucidated, but it is believed that they reduce the lymphocytic infiltrate and TNF expression. […] The understanding of the pathogenesis of vitiligo develops in parallel with the knowledge of the genetic regulation of the phenomena linked to OS and the cutaneous immune response. […] The integration of these theories is the main challenge in the construction of pathophysiological models.

• #50 SciELO Brasil – Update on the pathogenesis of vitiligo Update on the pathogenesis of vitiligo

  https://www.scielo.br/j/abd/a/rGFjzRRxSLpMJ7y8Cxdz9HD/

  The type I IFN pathway is a key point for the start of the vitiligo immune response. […] The Janus kinase/signal transducers and transcription activators (JAK/STAT) pathway participate in the immunopathogenesis of vitiligo through its interaction with IFN. […] In conclusion, the pathogenesis of vitiligo results from an interaction of elements (multifactorial), which suggests a genetic susceptibility basis, affected by environmental factors, oxidative stress, psychological factors, and patterns of autoimmune response.

• #51 Update on the pathogenesis of vitiligo | Anais Brasileiros de Dermatologia

  https://www.anaisdedermatologia.org.br/en-update-on-pathogenesis-vitiligo-articulo-S0365059622000654

  The lesions are caused by effector CD8+ T-lymphocytes in the initial or active phase of the disease and by recirculating and resident memory CD8+T (TEM) lymphocytes in the stable phase. […] The mechanism of aggression is based on the production of inflammatory cytokines such as TNF and IFN, in addition to the release of granzymes and perforins, which cause direct damage to melanocytes. […] The Janus kinase/signal transducers and transcription activators (JAK/STAT) pathway participate in the immunopathogenesis of vitiligo through its interaction with IFN. […] The exact mechanism by which topical therapies with corticosteroids and calcineurin inhibitors affect the disease pathogenesis has yet to be fully elucidated, but it is believed that they reduce the lymphocytic infiltrate and TNF expression.

• #52

  https://link.springer.com/article/10.1007/s13555-020-00447-y

  Several data link vitiligo to a type I IFN signature. […] The binding of IFN- to its receptor induces the Janus kinase/signal transducer and activator of the transcription (JAK/STAT) pathway, in particular JAK1-2 and STAT1 activation. […] Recent studies in vitiligo have demonstrated that IFN- induces the production of the CXCR3 ligands CXCL9 and CXCL10 by keratinocytes, thereby amplifying inflammation and the recruitment of immune cells expressing CXCR3 that will further promote vitiligo progression. […] Cytokines are key mediators of melanocyte loss in vitiligo and participate at every step of the pathogenesis of this disease. […] JAK inhibitors are showing promising results, but their broader effects can not reveal which predominant pathways are fully involved in the disease, supporting the notion that an intricate combination of multiple immune pathways are involved in the initiation and progression of the disease.

• #53

  https://journals.lww.com/jdpa/fulltext/2025/01910/understanding_the_mechanism_of_disease_of_vitiligo.7.aspx

  Melanocyte stress leads to activation of a subset of innate immune cells that perform a variety of functions after initial damage of melanocytes. […] Interactions between immune cells lead to activation and recruitment of cytotoxic CD8+ T cells that target melanocytes. […] CD8+ T cells predominantly infiltrate perilesional skin, where they produce interferon-gamma (IFN-), an important cytokine that is pivotal in driving vitiligo pathogenesis. […] JAK-STAT signaling by IFN- leads to the production of chemokines including C-X-C motif chemokine ligand 9 and C-X-C motif chemokine ligand 10 in the skin, which promote recruitment and localization of CD8+ T cells expressing C-X-C motif chemokine receptor 3 that are specific for melanocytes. […] Increased production of IFN- also establishes a positive feedback loop that maintains chemokine production from keratinocytes and continuous recruitment of CD8+ T cells to the skin, leading to the destruction of melanocytes and subsequent skin depigmentation.

• #54

  https://journals.lww.com/jdpa/fulltext/2025/01910/understanding_the_mechanism_of_disease_of_vitiligo.7.aspx

  Melanocyte stress leads to activation of a subset of innate immune cells that perform a variety of functions after initial damage of melanocytes. […] Interactions between immune cells lead to activation and recruitment of cytotoxic CD8+ T cells that target melanocytes. […] CD8+ T cells predominantly infiltrate perilesional skin, where they produce interferon-gamma (IFN-), an important cytokine that is pivotal in driving vitiligo pathogenesis. […] JAK-STAT signaling by IFN- leads to the production of chemokines including C-X-C motif chemokine ligand 9 and C-X-C motif chemokine ligand 10 in the skin, which promote recruitment and localization of CD8+ T cells expressing C-X-C motif chemokine receptor 3 that are specific for melanocytes. […] Increased production of IFN- also establishes a positive feedback loop that maintains chemokine production from keratinocytes and continuous recruitment of CD8+ T cells to the skin, leading to the destruction of melanocytes and subsequent skin depigmentation.

• #55 :: AD :: Annals of Dermatology

  https://anndermatol.org/DOIx.php?id=10.5021/ad.23.065

  Increased oxidative stress not only damages melanocytes, but also induces autoimmunity through the upregulation of the calreticulin expression and translocation to the cell membrane. […] These findings indicate that skin resident cells including keratinocytes and dermal fibroblasts may play a key role in regulating the microenvironment of vitiligo immunity. […] Correctly understanding the mechanisms for ROS accumulation and the associated types of unique autoimmunity is expected to lead to the proper clinical management of vitiligo. […] Recent studies have shown that the local immune environment generated by vitiligo lesions plays an important role in the onset and maintenance of vitiligo. […] IFN–signals activate the intracellular JAK-signal transducer and activator (STAT) 1 pathway to produce CXCL9/10 in keratinocytes, after which cytotoxic T cells expressing the receptor CXCR3 migrate to the epidermis and release molecules, such as granzyme B and perforin, to attack melanocytes. […] Furthermore, the mechanism by which IFN- reactivates keratinocytes has been clarified; therefore, JAK-targeted therapeutic applications have come to be used for the pathology of the IFN–JAK-STAT1 axis.

• #56

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9263675/

  Vitiligo is a complex disease whose pathogenesis results from the interaction of genetic components, metabolic factors linked to cellular oxidative stress, melanocyte adhesion to the epithelium, and immunity (innate and adaptive), which culminate in aggression against melanocytes. […] In vitiligo, melanocytes are more sensitive to oxidative damage, leading to the increased expression of proinflammatory proteins such as HSP70. […] The lower expression of epithelial adhesion molecules, such as DDR1 and E-cadherin, facilitates damage to melanocytes and exposure of antigens that favor autoimmunity. […] Activation of the type 1-IFN pathway perpetuates the direct action of CD8+ cells against melanocytes, facilitated by regulatory T-cell dysfunction. […] The identification of several genes involved in these processes sets the stage for disease development and maintenance.

• #57 Update on the pathogenesis of vitiligo | Anais Brasileiros de Dermatologia (Portuguese)

  http://www.anaisdedermatologia.org.br/pt-update-on-pathogenesis-vitiligo-avance-S0365059622000654

  Vitiligo is a complex disease whose pathogenesis results from the interaction of genetic components, metabolic factors linked to cellular oxidative stress, melanocyte adhesion to the epithelium, and immunity (innate and adaptive), which culminate in aggression against melanocytes. […] In vitiligo, melanocytes are more sensitive to oxidative damage, leading to the increased expression of proinflammatory proteins such as HSP70. […] The lower expression of epithelial adhesion molecules, such as DDR1 and E-cadherin, facilitates damage to melanocytes and exposure of antigens that favor autoimmunity. […] Activation of the type 1-IFN pathway perpetuates the direct action of CD8+ cells against melanocytes, facilitated by regulatory T-cell dysfunction. […] The identification of several genes involved in these processes sets the stage for disease development and maintenance.

• #58 Highlights in pathogenesis of vitiligo

  https://www.wjgnet.com/2307-8960/full/v3/i3/221.htm

  For the first time, Bagherani et al and Yaghoobi et al pointed the probable association which might be present between ZAG and vitiligo. It was suggested that the pathogenesis of vitiligo could be attributed to decrease in ZAG as follows: Studies have demonstrated that ZAG is acting as a keratinocyte-derived factor influencing melanocyte proliferation and dendricity. […] Melanocytes in vitiligo have an intrinsic defect leading to their death. They demonstrate different abnormalities, including abnormal rough endoplasmic reticulum or deficiency of unidentified melanocyte growth factors such as basic fibroblast growth factor (bFGF) and decrease in the number of melanocytes expressing the c-kit receptor in lesional skin. […] Recently, malfunctioning melanocytes found in vitiliginous lesions. Electron microscopy, reverse transcription PCR (polymerase chain reaction) and southern blotting experiments revealed sporadic survival of melanocyte in vitiliginous lesions. Thus, this points to presence of immature melanocyte precursors/stem cells. Now, 2 pathways have been supposed for melanocytes loss: highly programmed death by apoptosis and accelerated cell senescence.

• #59 Highlights in pathogenesis of vitiligo

  https://www.wjgnet.com/2307-8960/full/v3/i3/221.htm

  Gauthier et al in 2003 mentioned that NSV occurs due to melanocytorrhagy, or a chronic melanocytes detachment and loss caused by trauma and other stressors include catecholamines, ROS, or autoimmune elements. This theory combined the concepts from other theories mentioned before to elaborate a single integrated explanation of vitiligo pathogenesis. […] Despite all the mentioned theories are attractive, it is likely that vitiligo is a result of the convergence of these pathological pathways. Most experts agree that vitiligo may be a syndrome with a multi-factorial etiology rather than a single entity.

• #60 Endoplasmic Reticulum Dysfunction: An Emerging Mechanism of Vitiligo P | CCID

  https://www.dovepress.com/endoplasmic-reticulum-dysfunction-an-emerging-mechanism-of-vitiligo-pa-peer-reviewed-fulltext-article-CCID

  The endoplasmic reticulum (ER) is an important organelle associated with the synthesis, folding, and transporting of proteins. […] The importance of oxidative stress in the pathogenesis of vitiligo has been highlighted in recent years. […] Oxidative stress is considered to be an important link in the pathogenesis of vitiligo, which suggests ER may also be indispensable in the vitiligo pathogenesis. […] All of this evidence suggests and reinforces that ER is also involved in the pathogenesis of vitiligo. […] Therefore, this review summarized the current progress of ER and its involvement in vitiligo, and also focused on its function and possible mechanisms in vitiligo pathogenesis from cellular level to organelle level. […] The absence of functional melanocytes is the key process in vitiligo, which leads to pigmented lesions.

• #61 Endoplasmic Reticulum Dysfunction: An Emerging Mechanism of Vitiligo P | CCID

  https://www.dovepress.com/endoplasmic-reticulum-dysfunction-an-emerging-mechanism-of-vitiligo-pa-peer-reviewed-fulltext-article-CCID

  However, there is still no precise explanation for the reason why melanocytes disappear. […] In addition, the dilation of the RER was also found in the vitiligo mouse model. […] Recently, clinical trials revealed that the association of XBP1 polymorphisms and increased XBP1 expression has been observed in Gujarat and Chinese population, further confirming its involvement in ER stress and the immune-mediated pathogenesis of vitiligo. […] Therefore, more and more researchers have demonstrated the ER morphological and genetic abnormalities of melanocytes in vitiligo. […] Interestingly, ERS could not only induce melanocyte damage but also was reported to be associated with melanogenesis. […] The role of mitochondria in ROS production and immunity makes it indispensable in vitiligo pathogenesis.

• #62 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20240910/Researchers-uncover-clues-to-the-mechanism-behind-vitiligo.aspx

  Skin pigmentation disorders affect people across the world. One of them, vitiligo, is said to have a worldwide incidence of 1-2%. What causes the loss of pigmentation in vitiligo has long been unclear, but an Osaka Metropolitan University-led team has uncovered clues to the mechanism behind the disorder. […] They also discovered an overexpression of an enzyme in vitiligo-affected skin. Too much of this enzyme, matrix metalloproteinase 2 (MMP2), might be causing the disturbance to the basement membrane. […] An experiment using model mice with vitiligo-like depigmentation showed recovery of pigment-producing cells when MMP2 was suppressed. […] The results of this study potentially provide a new method for the treatment of vitiligo. In particular, by suppressing MMP2, the hope is that pigment-producing cells will return to the skin.

• #63 The Neuronal Theory in the Pathogenesis of Vitiligo: Past and Present | Auctores

  https://auctoresonline.org/article/the-neuronal-theory-in-the-pathogenesis-of-vitiligo-past-and-present

  The exact pathogenesis of vitiligo is still not fully understood, hence there are many theories and hypothesis been proposed including the autoimmune, Neuronal, melanocyte self-destruction, or defective adhesion, degenerative, composite and convergence. Non can explain all pathophysiology, however, lately it is believed that there is an overlap or link between some of these theories to fully understand the complete picture of vitiligo pathogenesis. […] The Neuronal theory was first introduced by Lerner in 1959. He postulated the neuronal theory in the pathogenesis of vitiligo. He proposed that the nerve ending in the skin release substance which can be cytotoxic leading to the destruction of the Melanocytes. […] In 1994 the Neuronal theory been boosted with the discovery of the link of Neuropeptides and in particular Neuropeptide Y (NPY) in the pathogenesis of vitiligo. It was postulated that upon specific factors the release of such peptides can initiate a cascade of events where it can trigger the immune system in a process leading to the destruction of the melanocytes in a genetically predisposed individuals. Hence this has linked the neuronal and the autoimmune theories in the pathogenesis of vitiligo.

• #64 The Neuronal Theory in the Pathogenesis of Vitiligo: Past and Present | Auctores

  https://auctoresonline.org/article/the-neuronal-theory-in-the-pathogenesis-of-vitiligo-past-and-present

  The exact pathogenesis of vitiligo is still not fully understood, hence there are many theories and hypothesis been proposed including the autoimmune, Neuronal, melanocyte self-destruction, or defective adhesion, degenerative, composite and convergence. Non can explain all pathophysiology, however, lately it is believed that there is an overlap or link between some of these theories to fully understand the complete picture of vitiligo pathogenesis. […] The Neuronal theory was first introduced by Lerner in 1959. He postulated the neuronal theory in the pathogenesis of vitiligo. He proposed that the nerve ending in the skin release substance which can be cytotoxic leading to the destruction of the Melanocytes. […] In 1994 the Neuronal theory been boosted with the discovery of the link of Neuropeptides and in particular Neuropeptide Y (NPY) in the pathogenesis of vitiligo. It was postulated that upon specific factors the release of such peptides can initiate a cascade of events where it can trigger the immune system in a process leading to the destruction of the melanocytes in a genetically predisposed individuals. Hence this has linked the neuronal and the autoimmune theories in the pathogenesis of vitiligo.

• #65 The Neuronal Theory in the Pathogenesis of Vitiligo: Past and Present | Auctores

  https://auctoresonline.org/article/the-neuronal-theory-in-the-pathogenesis-of-vitiligo-past-and-present

  The concept of neuronal involvement in vitiligo is largely based on clinical observations. […] Lerner (1) postulated that vitiligo probably resulted from increased output at the peripheral nerve endings of a substance that lightens melanocytes. […] The neuronal influence on the skin color of certain animals is well known. […] The clinical observation of a link between the nervous system and vitiligo initiated many physiological and biomedical studies. […] Biochemical studies have showed that pathways for the metabolism of the amino acid tyrosine and its oxidative derivative, dopa, are the substrates for both melanin and the neurotransmitters adrenaline and non-adrenaline. […] Melanocytes and nerve cells are both derived from the neural crest and melanocytes are thought to migrate towards the epidermis at the third trimester.

• #66 The Neuronal Theory in the Pathogenesis of Vitiligo: Past and Present | Auctores

  https://auctoresonline.org/article/the-neuronal-theory-in-the-pathogenesis-of-vitiligo-past-and-present

  The concept of neuronal involvement in vitiligo is largely based on clinical observations. […] Lerner (1) postulated that vitiligo probably resulted from increased output at the peripheral nerve endings of a substance that lightens melanocytes. […] The neuronal influence on the skin color of certain animals is well known. […] The clinical observation of a link between the nervous system and vitiligo initiated many physiological and biomedical studies. […] Biochemical studies have showed that pathways for the metabolism of the amino acid tyrosine and its oxidative derivative, dopa, are the substrates for both melanin and the neurotransmitters adrenaline and non-adrenaline. […] Melanocytes and nerve cells are both derived from the neural crest and melanocytes are thought to migrate towards the epidermis at the third trimester.

• #67 Highlights in pathogenesis of vitiligo

  https://www.wjgnet.com/2307-8960/full/v3/i3/221.htm

  Gauthier et al in 2003 mentioned that NSV occurs due to melanocytorrhagy, or a chronic melanocytes detachment and loss caused by trauma and other stressors include catecholamines, ROS, or autoimmune elements. This theory combined the concepts from other theories mentioned before to elaborate a single integrated explanation of vitiligo pathogenesis. […] Despite all the mentioned theories are attractive, it is likely that vitiligo is a result of the convergence of these pathological pathways. Most experts agree that vitiligo may be a syndrome with a multi-factorial etiology rather than a single entity.

• #68 Vitiligo, from Pathogenesis to Therapeutic Advances: State of the Art

  https://www.mdpi.com/1422-0067/24/5/4910

  Vitiligo is an acquired hypopigmentation of the skin due to a progressive selective loss of melanocytes; it has a prevalence of 1–2% and appears as rounded, well-demarcated white macules. The etiopathology of the disease has not been well defined, but multiple factors contribute to melanocyte loss: metabolic abnormalities, oxidative stress, inflammation, and autoimmunity. Therefore, a convergence theory was proposed that combines all existing theories into a comprehensive one in which several mechanisms contribute to the reduction of melanocyte viability. […] Although each of these pathogenetic hypotheses are still under discussion, there is now an agreement on the autoimmune and oxidative stress theories as leading processes in vitiligo pathogenesis. […] The precise etiology and pathophysiology are complex, and there is still much debate about the various theories on the loss of melanocyte function. Multiple pathophysiological mechanisms, including genetics, autoimmunity, oxidative stress, and neurological system dysfunction, have been proposed.

• #69 Vitiligo: From Pathogenesis to Treatment

  https://www.mdpi.com/2077-0383/13/17/5225

  While the immunological mechanism between both forms of vitiligo largely overlaps, the main cause of segmental vitiligo is likely somatic mosaicism, which causes a shorter duration of the inflammatory phase and different treatment options (e.g., pigment cell transplantation). […] This strengthens the convergence theory that multiple pathways interact in the development of vitiligo, although the autoimmune mechanisms are currently considered to be most crucial. […] Cytotoxic T cells play a significant role in vitiligo by targeting epidermal melanocytes. However, these cells are also found in ‘healthy’ individuals and are not exclusively associated with vitiligo. […] In vitiligo patients, this balance is shifted, leading to an increased activation of these cytotoxic T cells. […] Vitiligo-like lesions have been observed during anti-Programmed death-ligand 1 (PD-L1) treatment (pembrolizumab) in up to 25% of melanoma patients and are associated with improved survival rates.

• #70

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9263675/

  The Janus kinase/signal transducers and transcription activators (JAK/STAT) pathway participate in the immunopathogenesis of vitiligo through its interaction with IFN. […] The exact mechanism by which topical therapies with corticosteroids and calcineurin inhibitors affect the disease pathogenesis has yet to be fully elucidated, but it is believed that they reduce the lymphocytic infiltrate and TNF expression. […] The understanding of the pathogenesis of vitiligo develops in parallel with the knowledge of the genetic regulation of the phenomena linked to OS and the cutaneous immune response. […] The integration of these theories is the main challenge in the construction of pathophysiological models.

• #71 Vitiligo, from Pathogenesis to Therapeutic Advances: State of the Art

  https://www.mdpi.com/1422-0067/24/5/4910

  The importance of autoimmunity and genetics in the disease’s development is demonstrated by the presence of several preclinical studies involving IL-15 pathways; studies targeting the production of ROS, DAMPs, and antioxidant pathways or chemokine receptors; and stimulating melanocyte stem cells. […] There is still a long way to a comprehensive understanding of the pathophysiological mechanisms that cause vitiligo. It is certain that oxidative stress plays a crucial role in melanocyte loss. […] Vitiligo has a complex pathogenetic mechanism in which multiple pathways are involved so combination therapies appear to be more effective than those targeting a single pathway.

• #72

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9263675/

  The Janus kinase/signal transducers and transcription activators (JAK/STAT) pathway participate in the immunopathogenesis of vitiligo through its interaction with IFN. […] The exact mechanism by which topical therapies with corticosteroids and calcineurin inhibitors affect the disease pathogenesis has yet to be fully elucidated, but it is believed that they reduce the lymphocytic infiltrate and TNF expression. […] The understanding of the pathogenesis of vitiligo develops in parallel with the knowledge of the genetic regulation of the phenomena linked to OS and the cutaneous immune response. […] The integration of these theories is the main challenge in the construction of pathophysiological models.

• #73 Update on the pathogenesis of vitiligo | Anais Brasileiros de Dermatologia

  https://www.anaisdedermatologia.org.br/en-update-on-pathogenesis-vitiligo-articulo-S0365059622000654

  The lesions are caused by effector CD8+ T-lymphocytes in the initial or active phase of the disease and by recirculating and resident memory CD8+T (TEM) lymphocytes in the stable phase. […] The mechanism of aggression is based on the production of inflammatory cytokines such as TNF and IFN, in addition to the release of granzymes and perforins, which cause direct damage to melanocytes. […] The Janus kinase/signal transducers and transcription activators (JAK/STAT) pathway participate in the immunopathogenesis of vitiligo through its interaction with IFN. […] The exact mechanism by which topical therapies with corticosteroids and calcineurin inhibitors affect the disease pathogenesis has yet to be fully elucidated, but it is believed that they reduce the lymphocytic infiltrate and TNF expression.

• #74 Update on the pathogenesis of vitiligo | Anais Brasileiros de Dermatologia

  https://www.anaisdedermatologia.org.br/en-update-on-pathogenesis-vitiligo-articulo-S0365059622000654

  The three emerging vitiligo therapeutic classes that are at the most advanced stage of development and are associated with the most important pathogenic pathways are the tyrosine kinase inhibitors (e.g., JAK1, JAK2, JAK3, TYK2), anti-IL15, and mutant HSP70. […] In conclusion, the pathogenesis of vitiligo results from an interaction of elements (multifactorial), which suggests a genetic susceptibility basis, affected by environmental factors, oxidative stress, psychological factors, and patterns of autoimmune response.

• #75

  https://link.springer.com/article/10.1007/s13555-020-00447-y

  Vitiligo is a chronic inflammatory skin disease leading to the loss of epidermal melanocytes. […] Recent insights into the understanding of the immune pathogenesis of the disease have led to the identification of several therapeutic targets and the development of targeted therapies that are now being tested in clinical trials. […] A better understanding of the immune pathogenesis of vitiligo has led to the identification and development of targeted therapies. […] Targeting innate immune pathways through the inhibition of danger signals, such as HSP70, represents an interesting approach for the treatment of vitiligo. […] Resident memory T cells are involved in the recurrence of vitiligo and could be targeted by blocking interleukin-15. […] Trials involving JAK inhibitors, which inhibit the effects of several pro-inflammatory cytokines, have shown promising results in vitiligo.

• #76 Mechanism of Action | OPZELURA® (ruxolitinib) HCP

  https://www.opzelurahcp.com/vitiligo/mechanism-of-action

  DEPIGMENTATION IN VITILIGO IS DRIVEN BY IFN- MEDIATED JAK-STAT SIGNALING2,4 […] IFN- mediated JAK-STAT signaling is thought to drive an inflammatory cycle, creating a hostile environment in which CD8+ T-cells target and destroy melanocytes2,4,5 […] Continued signaling by IFN- and CXCL9/10 attracts more autoreactive T-cells, perpetuating an inflammatory cycle of melanocyte destruction2,6 […] OPZELURA is thought to inhibit IFN- mediated JAK-STAT signaling, a key driver of depigmentation in vitiligo1-3 […] OPZELURA is a topical JAK inhibitor that regulates IFN- mediated JAK-STAT signaling, which is thought to reduce CD8+ T-cell mediated destruction of melanocytes.1,2,6,8 […] Ruxolitinib, the active ingredient in OPZELURA, binds to the JAK1 and JAK2 enzymes and is thought to inhibit IFN- mediated JAK-STAT signaling1-3,9.

• #77

  https://journals.lww.com/jdpa/fulltext/2025/01910/understanding_the_mechanism_of_disease_of_vitiligo.7.aspx

  During vitiligo progression, a subset of the CD8+ T cells in the skin transform into skin resident memory T cells. […] The activity and survival of skin resident memory T cells is maintained by interleukin-15 (IL-15), a cytokine that utilizes the JAK-STAT signaling pathway. […] Resident memory CD8+ T cells remain in the skin indefinitely, causing persistent depigmentation as well as disease relapse after treatment discontinuation. […] Blocking crucial steps of the disease process, such as IFN- or IL-15 signaling, may halt skin depigmentation and allow new melanocytes to migrate into depigmented lesions, leading to gradual repigmentation over time. […] Repigmentation often initiates from hair follicles, which serve as a reservoir for stem cells that differentiate into melanoblasts and give rise to new melanocytes.

• #78

  https://journals.lww.com/jdpa/fulltext/2025/01910/understanding_the_mechanism_of_disease_of_vitiligo.7.aspx

  Time to repigmentation depends on the location of depigmented skin and the type of treatment, among other factors. […] Because vitiligo is a chronic autoimmune disease, long-term treatment is often required to obtain and maintain repigmentation. […] If treatment is withdrawn following repigmentation, reactivation of skin resident memory T cells is likely to result in disease relapse since the immune response is no longer limited. […] Currently, available treatments do not permanently modify disease mechanisms, and stopping treatment may lead to disease relapse.

• #79 SciELO Brasil – Update on the pathogenesis of vitiligo Update on the pathogenesis of vitiligo

  https://www.scielo.br/j/abd/a/rGFjzRRxSLpMJ7y8Cxdz9HD/

  The type I IFN pathway is a key point for the start of the vitiligo immune response. […] The Janus kinase/signal transducers and transcription activators (JAK/STAT) pathway participate in the immunopathogenesis of vitiligo through its interaction with IFN. […] In conclusion, the pathogenesis of vitiligo results from an interaction of elements (multifactorial), which suggests a genetic susceptibility basis, affected by environmental factors, oxidative stress, psychological factors, and patterns of autoimmune response.

• #80 Update on the pathogenesis of vitiligo | Anais Brasileiros de Dermatologia

  https://www.anaisdedermatologia.org.br/en-update-on-pathogenesis-vitiligo-articulo-S0365059622000654

  The three emerging vitiligo therapeutic classes that are at the most advanced stage of development and are associated with the most important pathogenic pathways are the tyrosine kinase inhibitors (e.g., JAK1, JAK2, JAK3, TYK2), anti-IL15, and mutant HSP70. […] In conclusion, the pathogenesis of vitiligo results from an interaction of elements (multifactorial), which suggests a genetic susceptibility basis, affected by environmental factors, oxidative stress, psychological factors, and patterns of autoimmune response.

• #81 Update on the pathogenesis of vitiligo | Anais Brasileiros de Dermatologia (Portuguese)

  http://www.anaisdedermatologia.org.br/pt-update-on-pathogenesis-vitiligo-avance-S0365059622000654

  The type I IFN pathway is a key point for the start of the vitiligo immune response. […] The activation of innate immunity triggered by damage to melanocytes affected by oxidative stress promotes cytokine secretion and antigen presentation, resulting in the adaptive immune system activation, in which autoreactive T-cells amplify damage to melanocytes in vitiligo-affected skin. […] The exact mechanism by which topical therapies with corticosteroids and calcineurin inhibitors affect the disease pathogenesis has yet to be fully elucidated, but it is believed that they reduce the lymphocytic infiltrate and TNF expression. […] The understanding of the pathogenesis of vitiligo develops in parallel with the knowledge of the genetic regulation of the phenomena linked to OS and the cutaneous immune response. […] In conclusion, the pathogenesis of vitiligo results from an interaction of elements (multifactorial), which suggests a genetic susceptibility basis, affected by environmental factors, oxidative stress, psychological factors, and patterns of autoimmune response.

• #82 :: AD :: Annals of Dermatology

  https://anndermatol.org/DOIx.php?id=10.5021/ad.23.065

  Increased oxidative stress not only damages melanocytes, but also induces autoimmunity through the upregulation of the calreticulin expression and translocation to the cell membrane. […] These findings indicate that skin resident cells including keratinocytes and dermal fibroblasts may play a key role in regulating the microenvironment of vitiligo immunity. […] Correctly understanding the mechanisms for ROS accumulation and the associated types of unique autoimmunity is expected to lead to the proper clinical management of vitiligo. […] Recent studies have shown that the local immune environment generated by vitiligo lesions plays an important role in the onset and maintenance of vitiligo. […] IFN–signals activate the intracellular JAK-signal transducer and activator (STAT) 1 pathway to produce CXCL9/10 in keratinocytes, after which cytotoxic T cells expressing the receptor CXCR3 migrate to the epidermis and release molecules, such as granzyme B and perforin, to attack melanocytes. […] Furthermore, the mechanism by which IFN- reactivates keratinocytes has been clarified; therefore, JAK-targeted therapeutic applications have come to be used for the pathology of the IFN–JAK-STAT1 axis.

• #83 Vitiligo pathogenesis and emerging treatments

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5362109/

  Genome-wide association studies have identified multiple risk alleles in patients with vitiligo, and most are associated with immune regulation. […] Melanocyte defects contribute to initiating autoimmunity in vitiligo. […] Environmental stressors, especially chemical phenols that mimic the amino acid tyrosine and the products that contain them, can induce and exacerbate vitiligo. […] A better understanding of the key pathways involved in vitiligo onset and progression will enable us to develop treatments that have greater efficacy and a good safety profile.

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