Materiały źródłowe

• #1 Lichen Planus – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK526126/

  Lichen planus is an idiopathic disease whose pathogenesis is not fully understood; however, it appears to represent a T-cell-mediated autoimmune disease. The prevailing theory is that exposure to an exogenous agent such as a virus, drug, or contact allergen alters epidermal self-antigens, leading to the activation of cytotoxic T cells. The altered self-antigens cross-react with normal self-antigens on basal keratinocytes, resulting in T-cell targeting and apoptosis. […] Current understanding suggests that the immunopathogenesis of lichen planus is caused by cell-mediated cytotoxicity, particularly cytotoxic T lymphocytes, whose activity is further influenced by TH1 and the interleukin 23/TH17 axis. Other immunocytes and inflammatory pathways complement these mechanisms.

• #2 Comprehensive Insight into Lichen Planus Immunopathogenesis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9918135/

  Lichen planus is a chronic disease affecting the skin, appendages, and mucous membranes. […] The etiology of lichen planus is not entirely understood. Yet, immune-mediated mechanisms have been recognized since environmental factors such as hepatitis virus infection, mechanical trauma, psychological stress, or microbiome changes can trigger the disease in genetically susceptible individuals. According to current understanding, lichen planus immunopathogenesis is caused by cell-mediated cytotoxicity, particularly cytotoxic T lymphocytes, whose activity is further influenced by Th1 and IL-23/Th-17 axis. However, other immunocytes and inflammatory pathways complement these mechanisms. […] The LP pathogenesis is, in a certain part, similar to that of another related disease, psoriasis. […] Reported data indicate that LP immunopathogenesis is primarily mediated by cell-mediated immune mechanisms, with T lymphocytes playing a pivotal role.

• #2 Comprehensive Insight into Lichen Planus Immunopathogenesis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9918135/

  LP initiation, maintenance, and progression heavily depend on antigen-focused action, while the nonspecific and humoral mechanisms complement it to a lesser extent. […] Based on the current understanding, LP immunopathogenesis results from the T-cell-mediated immune or autoimmune response to the exogenous or self-altered antigens presented by antigen-presenting cells (APCs) such as dendritic cells (DCs) or keratinocytes. […] The ultimate effect of pro-inflammatory cytokines is the production of oxygen free radicals (ROS) that induce cell apoptosis. […] However, as already emphasized, Tc action is particularly significant in LP pathogenesis. […] Conducted studies indicate that granule exocytosis is a major route of cytotoxicity in humans, but others complement this mechanism at different stages of the disease.

• #3 Lichen planus – Wikipedia

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

  Lichen planus (LP) is a chronic inflammatory and autoimmune disease that affects the skin, nails, hair, and mucous membranes. […] The cause is unknown, but it is thought to be the result of an autoimmune process with an unknown initial trigger. […] An immune-mediated mechanism where basal keratinocytes are being targeted as foreign antigens by activated T cells, especially CD8+ T cells, has been proposed. […] Upregulation of intercellular adhesion molecule-1 (ICAM-1) and cytokines associated with T-helper 1 immune response, may also play an important role in the pathogenesis of lichen planus. […] Oral LP is considered to be a T-cell mediated chronic inflammatory tissue reaction that results in a cytotoxic reaction against epithelial basal cells. […] The inflammatory infiltrate in oral LP is primarily composed of CD8+ T cells.

• #4 Oral Lichen Planus: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1078327-overview

  Evidence suggests that OLP is a T-cellmediated autoimmune disease in which autocytotoxic CD8+ T cells trigger apoptosis of oral epithelial cells. […] The dense subepithelial mononuclear infiltrate in OLP is composed of T cells and macrophages, and there are increased numbers of intraepithelial T cells. Most T cells in the epithelium and adjacent to the damaged basal keratinocytes are activated CD8+ lymphocytes. Therefore, early in the formation of OLP lesions, CD8+ T cells may recognize an antigen associated with the major histocompatibility complex (MHC) class I on keratinocytes. After antigen recognition and activation, CD8+ cytotoxic T cells may trigger keratinocyte apoptosis. Activated CD8+ T cells (and possibly keratinocytes) may release cytokines that attract additional lymphocytes into the developing lesion.

• #5 Localization of T-cell subsets in cutaneous lichen planus: An insight into pathogenetic mechanism – Indian Journal of Dermatology, Venereology and Leprology

  https://ijdvl.com/localization-of-t-cell-subsets-in-cutaneous-lichen-planus-an-insight-into-pathogenetic-mechanism/

  We would like to report the results of our evaluation of T-cell subsets in cutaneous lichen planus (LP). […] The present study supports the primary role of CD8+ cytotoxic T cells in keratinocyte damage, since the dermo-epidermal infiltrate was seen to be composed predominantly of CD8+ T cells. The perivascular localization of CD4+ T cells is an indicator of the possible assistance offered to the cytotoxic CD8+ cells by secretion of Th1 cytokines. Keratinocyte damage by CD8+ T cells would lead to basement membrane disruption, paving way for the influx of more CD8+ T cells and further basal cell damage resulting in a vicious cycle leading to chronicity of the disease. […] In conclusion, cutaneous lichen planus is a T-cell mediated inflammatory disease with pathogenetic role of both CD8+ cytotoxic T cells and CD4+ helper T cells. There is a predominance of cytotoxic T cells in the dermo-epidermal infiltrate responsible for keratinocyte damage. Helper/ inducer CD4+ T cells are found in the perivascular dermal infiltrate, which may be assisting the cytotoxic cells in the keratinocyte damage.

• #6 Lichen planus – Wikipedia

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

  Activated CD8+ T cells induce keratinocyte apoptosis through various mechanisms such as secretion of tumor necrosis factor (TNF)-alpha, secretion of granzyme B, or Fas-Fas ligand interactions. […] Other mechanisms that have been proposed include: upregulation of matrix metalloproteinases that disrupt the epithelial basement membrane zone and allow entry of immune cells into the epidermis, the release of proinflammatory mediators and proteases by mast cells, and perturbations in the innate immune response that may involve toll-like receptors. […] Oral LP may also be caused by genetic factor which influence the immune function.

• #7 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Lichen-Planus-Causes.aspx

  Lichen planus is an autoimmune disease supposed to be mediated by cytotoxic CD8+ T lymphocytes directed against the basal cells of the oral mucosal epithelium. […] The sequence of events in LP includes: […] Expression of a non-self antigen by keratinocytes […] Detection of the antigen during immune surveillance or response to chemokines produces T-cell migration, mostly CD8+ cells, into the epithelium […] T-cells are activated either directly through antigen binding to MHC-1 on keratinocyte, or via activated CD4+ cells […] Further antigen presentation activates CD4+ helper T cells leading to further activation of CD8+ T cells […] Auto-cytotoxic CD8+ T cells target basal keratinocytes and produce apoptosis via various pathways such as tumor necrosis factor (TNF-).

• #8 Comprehensive Insight into Lichen Planus Immunopathogenesis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9918135/

  Increased levels of TNF- in sera and Fas-FasL, granzyme B, and perforin in the skin were previously found in LP patients compared to healthy controls, while recent research confirmed granulysin overexpression in the skin and peripheral blood of LP patients. […] While apoptosis of epithelial cells in LP is emphasized, the death of inflammatory cells is reduced, contributing to the inflammatory process’s progression. […] A possible Th17 lymphocyte plasticity change based on the surrounding milieu, as well as delicate balance and interconnections between Th1, Th17 and Treg lymphocytes, could have a decisive contribution to the LP pathogenesis. […] Excessive IL-23 and IL-17 expression in revealed LP patients compared to controls suggest a potential role of the IL-23/Th-17 axis in the LP pathogenesis. Indeed, several studies have already recognized IL-17 as a critical mediator of LP immunopathogenesis. […] These observations indicate that, in addition to the fundamental cytotoxic mechanisms, Th1 and IL-23/Th-17 inflammatory pathways have a central place in LP immunopathogenesis.

• #9 Comprehensive Insight into Lichen Planus Immunopathogenesis

  https://www.mdpi.com/1422-0067/24/3/3038

  Based on the current understanding, LP immunopathogenesis results from the T-cell-mediated immune or autoimmune response to the exogenous or self-altered antigens presented by antigen-presenting cells (APCs) such as dendritic cells (DCs) or keratinocytes. […] The ultimate effect of pro-inflammatory cytokines is the production of oxygen free radicals (ROS) that induce cell apoptosis. […] Increased levels of TNF-α in sera and Fas-FasL, granzyme B, and perforin in the skin were previously found in LP patients compared to healthy controls, while recent research confirmed granulysin overexpression in the skin and peripheral blood of LP patients. […] While apoptosis of epithelial cells in LP is emphasized, the death of inflammatory cells is reduced, contributing to the inflammatory process’s progression.

• #9 Comprehensive Insight into Lichen Planus Immunopathogenesis

  https://www.mdpi.com/1422-0067/24/3/3038

  A possible Th17 lymphocyte plasticity change based on the surrounding milieu, as well as delicate balance and interconnections between Th1, Th17 and Treg lymphocytes, could have a decisive contribution to the LP pathogenesis. […] Excessive IL-23 and IL-17 expression in revealed LP patients compared to controls suggest a potential role of the IL-23/Th-17 axis in the LP pathogenesis. Indeed, several studies have already recognized IL-17 as a critical mediator of LP immunopathogenesis.

• #10 Oral erosive lichen planus – a case report with a highlight on etiopathogeneses and immunomodulatory effect of tacrolimus in management of OELP – MedCrave online

  https://medcraveonline.com/MOJCR/oral-erosive-lichen-planus—a-case-report-with-a-highlight-on-etiopathogeneses-and-immunomodulatory-effect-of-tacrolimus-in-management-of-oelp.html

  Apart from there are many non-specific mechanisms may be involved in the pathogenesis of OLP, including The Heat Shock Proteins (HSPs), reactive oxygen species (ROS), stress, mast cell chemotaxis and degranulation stimulated by T-cell RANTES, endothelial cell adhesion molecule expression stimulated by mast cell TNF-a, T-cell MMP-9 activation by mast cell chymase, epithelial basement membrane disruption by mast cell proteases or T-cell MMP-9, keratinocyte apoptosis triggered by epithelial basement membrane disruption, intra-epithelial CD8+ T-cell migration through basement membrane breaks, inflammatory cell survival prolonged by T-cell RANTES and non-specific T-cell recruitment by keratinocyte-derived chemokines. […] The pathogenesis of OLP may involve both antigen-specific and non-specific mechanisms. […] In this disease mechanism, TACROLIMUS acts at the dephosphorylation stage thus obstructing it and bringing about phosphorylation. This ultimately decreases the activity of genes coding for various ILs which ceases the progress towards OLP like lesions.

• #11 Lichen Planus: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1123213-overview

  Associations have been noted between LP and hepatitis C virus (HCV) infection, chronic active hepatitis, and primary biliary cirrhosis. […] A workup for hepatitis C should be considered in patients with widespread or unusual presentations of LP. Onset or exacerbation of LP has also been linked to stressful events.

• #11 Lichen Planus: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1123213-overview

  Lichen planus (LP) is a cell-mediated immune response of unknown origin. […] Although the pathophysiology is unclear, it is an immunologically mediated reaction. […] LP is a cell-mediated immune response of unknown origin. It may be found with other diseases of altered immunity; such conditions include ulcerative colitis, alopecia areata, vitiligo, dermatomyositis, morphea, lichen sclerosus, and myasthenia gravis. […] The exact cause of LP has not been established, though the condition is known to be immunologically mediated. The initiating antigen is unclear; however, Langerhans cells process the antigen to T lymphocytes, resulting in an epidermotropic infiltrate. Histologically, the inflammation is described as a lichenoid infiltrate, effacing the dermoepidermal junction. […] Some patients with LP have a positive family history. It has been noted that affected families have an increased frequency of human leukocyte antigen (HLA)-B7. Others have found an association between idiopathic LP and HLA-DR1 and HLA-DR10; thus, LP may be influenced by a genetic predisposition.

• #12 Lichen Planus | AAFP

  https://www.aafp.org/pubs/afp/issues/2000/0601/p3319.html

  Lichen planus is an inflammatory mucocutaneous condition with characteristic violaceous polygonal flat-topped papules and plaques. […] The etiology of lichen planus is unknown, although many studies have investigated and support an immunologic pathogenesis. Lymphocytes, particularly T-cells, play a major role. […] While most cases of lichen planus are idiopathic, some are linked to medication use or hepatitis C virus (HCV) infection. […] Although the manner in which HCV infection predisposes patients to the development of lichen planus is unknown, some speculate that long-term infection may lead to an aberrant immunologic response.

• #13 Lichen planus: Symptoms, Types, and Treatment with Images — DermNet

  https://dermnetnz.org/topics/lichen-planus

  Lichen planus is a T-cell mediated autoimmune disorder in which inflammatory cells attack an unknown protein within the skin and mucosal keratinocytes. […] Vitamin D deficiency may be associated with oral lichen planus. Its association with other types of LP remains unexplored. […] Lichen planus can have a chronic remitting and relapsing course.

• #14 Oral lichenplanus: Etiology, pathogenesis, diagnosis, and management

  https://www.wjgnet.com/2218-6263/full/v4/i1/12.htm

  The activated CD8+ T cells trigger the apoptosis of basal keratinocytes by releasing tumor necrosis factor-, granzyme B and by FasFasL mediated apoptosis. This results in loss of integrity of basement membrane. […] Both endogenous and exogenous factors may cause cell-mediated immunity in a genetically susceptible patient and appears to play a major role in the pathogenesis of OLP. […] The association of OLP with chronic liver disease was first suggested by Mokni et al in 1991. […] Epidemiological evidences strongly suggest that Hepatitis C Virus may be an etiologic factor in OLP. […] Periods of psychological stress and anxiety are associated with aggravation of OLP in most of the studies conducted so far. […] Koebner phenomenon is a characteristic feature of cutaneous LP and is also observed in oral cavity.

• #15

  https://link.springer.com/article/10.1007/s40496-014-0022-y

  Oral lichen planus (OLP) is a predominantly T-cell mediated disease that shares clinical and histological features with chronic graft versus host disease. […] A strong body of evidence suggest that lichen planus (LP) is a T-cell-mediated disease. […] The lymphocytic infiltrate in OLP is composed almost exclusively of T-cells. […] In OLP inflammatory infiltrate there is an enrichment of CD45RO memory T cells that predominantly express Th1 cytokine. […] A key, and probably early, event in LP, is the genetically induced increased production of Th1 cytokines that seems peculiar to patients without HCV infection. […] Another key event in OLP pathogenesis is the recruitment of different subsets of dendritic cells (DCs), such as Langerhans cells, myeloid and plasmacytoid DCs. […] Attraction and migration of the activated T cells to the oral epithelium is further enhanced by intercellular adhesion molecules (ICAM-1 and VCAM), up-regulation of epithelial basement membrane extracellular matrix proteins, and potentially CXCR3 and CCR5 signaling pathways.

• #16 Toll-like receptor 9-positive plasmacytoid dendritic cells promote Th17 immune responses in oral lichen planus stimulated by epithelium-derived cathepsin K | Scientific Reports

  https://www.nature.com/articles/s41598-023-46090-3

  Oral lichen planus (OLP) is a chronic inflammatory disease associated with T cell infiltration. The crosstalk between oral epithelium and mucosal T cells was considered to be crucial in the pathogenesis of OLP. Cathepsin K (CTSK) was identified as one of common upregulated genes in the LE by DNA microarray. Recent studies showed that CTSK enhanced Toll-like receptor 9 (TLR9) signaling in antigen-presenting cells, leading to Th17 cell differentiation. The number of RORt-positive cells correlated with that of CTSK-positive cells in OLP tissues. CD123+ pDCs induced the production of Th17-related cytokines (IL-6, IL-23, and TGF-) upon stimulation with TLR9 agonist CpG DNA. Moreover, single cell RNA-sequencing analysis revealed that TLR9-positive pDCs enhanced in genes associated with Th17 cell differentiation in comparison with TLR9-negative pDCs. CTSK could induce Th17-related production of CD123+ pDCs via TLR9 signaling to promote the pathogenesis of OLP.

• #17 Toll-like receptor 9-positive plasmacytoid dendritic cells promote Th17 immune responses in oral lichen planus stimulated by epithelium-derived cathepsin K | Scientific Reports

  https://www.nature.com/articles/s41598-023-46090-3

  In this study, we selectively extracted the LE of BM specimens by LCM, and CTSK was identified as one of epithelium-derived Th-immune molecules in the LE by DNA microarray. CTSK is a lysosome cysteine protease that is primarily expressed in osteoclasts and involved in bone remodeling and resorption. In vivo studies demonstrated that CTSK plays a key role in the gene induction program regulated by TLR9 signaling, and CTSK-dependent TLR9 signaling in DCs contributes to cancer metastasis and autoimmune inflammation. […] Our current data indicate that TLR9-expressing pDCs in the subepithelial layer recognize self-derived DNA or viral DNA. Activated pDCs produce several Th17-related cytokines (IL-6, IL-23, and TGF-) via TLR9 signaling by CTSK released from the infected and injured LE, leading to chronic inflammation in OLP.

• #18 Lichen planus in children – Indian Journal of Dermatology, Venereology and Leprology

  https://ijdvl.com/lichen-planus-in-children/

  The exact etiology of lichen planus is unknown. Genetic linkage studies have been undertaken to establish HLA- association for lichen planus. Copeman et al found an association between familial LP and HLA- B7. In a subsequent study by White and Rostom in Arab people, an association of HLA- DR1 and DR10 with lichen planus was observed. The occurrence of LP in monozygotic twins indicates toward genetic linkage of LP. However, majority of the studies could not prove the genetic association for LP. […] No precipitating factors were observed in the study by Kanwar et al as well as by Handa and Sahoo. Similarly, no history of previous drug intake was elicited in any of their patients by Sharma and Maheshwari and Luis- Montoya et al. On the contrary, Nanda et al found a precipitating factors in 22% of their patients in form of upper respiratory tract infection in four and viral exanthem in one patient before the onset of LP.

• #19 The Functional Mechanism of MicroRNA in Oral Lichen Planus | JIR

  https://www.dovepress.com/the-functional-mechanism-of-microrna-in-oral-lichen-planus-peer-reviewed-fulltext-article-JIR

  MiRNAs are implicated in various physiological and pathological processes, including critical roles in inflammation and the immune response. […] The study of miRNAs is vital to understanding OLP. Therefore, in this review, we examine the role that miRNAs play in OLP and summarize their mechanisms and functions of miRNAs and future directions in therapeutic research. […] MiR-123, miR-647, and miR-31 may, through circ_003912, have a role in the pathogenesis of EOLP. […] The apoptosis of keratinocytes may be promoted by miR-122 in OLP. […] Further, changes in the expression of miR-21 and miR-125a may lead to malignant transformation. […] Inflammation-related disorders exhibit a strong link between miRNAs and cytokines. Because many miRNAs are involved in OLP with different expression levels, research on their roles in the pathogenesis of OLP is essential.

• #20

  https://link.springer.com/article/10.1007/s10753-024-02146-8

  While corticosteroids are commonly employed to alleviate OLP symptoms by suppressing immune cell activation and migration, their effects are often transient, and the disease frequently recurs. […] According to recent evidence, OLP patients have a higher likelihood of infection by periodontal pathogens compared to non-OLP patients, such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, major periodontal pathogens, being detected at higher levels. […] Bacteria continuously release nano-sized particles called extracellular vesicles (EVs) that mediate interactions between pathogens and host cells. […] Recently, bacterial EVs have been regarded as main culprits in causing oral and systemic diseases due to their capacity for inducing pro-inflammatory signaling cascades and mediating long-distance microbiota-host communication.

• #20

  https://link.springer.com/article/10.1007/s10753-024-02146-8

  Oral lichen planus (OLP) is a chronic inflammatory disease characterized by an intensive infiltration of cytotoxic T cells, which causes keratinocyte death. […] The pathogenic mechanism of OLP is still uncertain. […] Notably, EVs derived from key periodontal pathogens, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, were shown to induce an inflammatory response and activate STAT3 signaling pathways, closely mirroring the pathophysiological features observed in OLP. […] These results underscore the potential role of bacterial EVs in the pathogenesis of OLP and highlight STAT3 as a critical mediator in this process. […] Histopathologically, a strong subepithelial T lymphocyte infiltration and elevated levels of intra-epithelial T cells are observed in OLP lesions.

• #21

  https://link.springer.com/article/10.1007/s10753-024-02146-8

  Our analysis indicates that genes associated with bacterial responses are upregulated in OLP. […] Interestingly, when we analyzed publicly available dataset to compare the effects of EVs and LPS derived from Pg on the host cell transcriptome, our result revealed that Pg EVs had a much greater impact on gene expression than Pg LPS. […] Our study demonstrates that EVs from Pg and Aa can significantly upregulate pro-inflammatory cytokines such as TNF, IL6, IL8, and IL1 in keratinocytes, mimicking the inflammatory environment observed in OLP lesions. […] The upregulation of STAT3 in OLP lesions, as confirmed by our immunofluorescence and immunoblot assays, points to its potential role as a mediator of chronic inflammation in OLP. […] The ability of these EVs to transport bacterial antigens and inflammatory mediators most likely enhances the immune response, fostering the chronic inflammatory state that underpinning OLP pathogenesis. […] Further studies are needed to improve our understanding of OLP pathogenesis and develop more targeted therapeutic interventions.

• #22 Direct Immunofluorescence Studies in Lichen Planus – Turkish Journal of Pathology

  https://turkjpath.org/text.php?id=1892

  Lichen planus is a common, usually intensely pruritic, symmetrical, papulosquamous dermatosis. Direct immunofluorescence studies in patients with lichen planus shows deposition of multiple immunoglobulins and fibrin at the dermoepidermal junction and in the colloid bodies. […] LP is an immune mediated disease which on DIF studies shows a linear and shaggy broad band of staining with fibrinogen, immunoglobulins and complement along the DEJ. […] DIF studies in LP show deposition of immunoreactants and fibrin along the DEJ in a broad discontinuous and shaggy pattern along with colloid body deposition. […] The pattern of staining in LE is linear, granular, broad, discontinuous band-like but it may also be smooth and continuous in occasional cases. […] The most common pattern in both diseases is CB plus DEJ. Although both LP and LE show overlapping results regarding the type of immunoglobulin deposition on DIF, the pattern of deposition makes the difference. […] The shaggy irregular deposits are characteristic of LP.

• #23 What Is Oral Lichen Planus? – Consensus: AI Search Engine for Research

  https://consensus.app/home/blog/what-is-oral-lichen-planus/

  Oral Lichen Planus (OLP) is a chronic mucocutaneous disease that primarily affects the oral cavity. It is characterized by its immune-mediated pathogenesis and is commonly seen in middle-aged and elderly females. […] The pathogenesis of OLP involves immune-mediated mechanisms, and it is considered an autoimmune condition. […] Further research is needed to fully understand the pathogenesis of OLP and to develop more targeted and effective treatment protocols.

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