Materiały źródłowe

• #1 Psoriasis Pathogenesis and Treatment

  https://www.mdpi.com/1422-0067/20/6/1475

  Research on psoriasis pathogenesis has largely increased knowledge on skin biology in general. In the past 15 years, breakthroughs in the understanding of the pathogenesis of psoriasis have been translated into targeted and highly effective therapies providing fundamental insights into the pathogenesis of chronic inflammatory diseases with a dominant IL-23/Th17 axis. This review discusses the mechanisms involved in the initiation and development of the disease, as well as the therapeutic options that have arisen from the dissection of the inflammatory psoriatic pathways. […] The hallmark of psoriasis is sustained inflammation that leads to uncontrolled keratinocyte proliferation and dysfunctional differentiation. The histology of the psoriatic plaque shows acanthosis (epidermal hyperplasia), which overlies inflammatory infiltrates composed of dermal dendritic cells, macrophages, T cells, and neutrophils. Neovascularization is also a prominent feature. The inflammatory pathways active in plaque psoriasis and the rest of the clinical variants overlap, but also display discrete differences that account for the different phenotype and treatment outcomes.

• #2 Cellular mechanisms of psoriasis pathogenesis | CCID

  https://www.dovepress.com/cellular-mechanisms-of-psoriasis-pathogenesis-a-systemic-review-peer-reviewed-fulltext-article-CCID

  Psoriasis is a common inflammatory skin disease characterized by abnormal proliferation of epidermal keratinocytes and massive infiltration of inflammatory cells. Many kinds of cells, including keratinocytes, T lymphocytes, dendritic cells, neutrophils, and macrophages, are reported to play critical roles in the pathogenesis and progression of psoriasis. […] Psoriasis is characterized by hyperproliferation and abnormal differentiation of keratinocytes, and massive infiltration of inflammatory immune cells. […] Psoriasis is now considered to be caused by immune abnormalities, which are triggered by genetic and environmental factors. […] Keratinocytes, as well as a variety of immune cells, including T cells, plasmacytoid dendritic cells (pDCs), myeloid dendritic cells (mDCs), neutrophils, and macrophages, work together to form an inflammatory circuit to contribute to the pathogenesis and development of psoriasis.

• #3 Psoriasis Pathogenesis and Treatment

  https://www.mdpi.com/1422-0067/20/6/1475

  Disturbances in the innate and adaptive cutaneous immune responses are responsible for the development and sustainment of psoriatic inflammation. An activation of the innate immune system driven by endogenous danger signals and cytokines characteristically coexists with an autoinflammatory perpetuation in some patients, and T cell-driven autoimmune reactions in others. Thus, psoriasis shows traits of an autoimmune disease on an (auto)inflammatory background, with both mechanisms overlapping and even potentiating one another. […] The main clinical findings in psoriasis are evident at the outermost layer of the skin, which is made up of keratinocytes. However, the development of the psoriatic plaque is not restricted to inflammation in the epidermal layer, but rather is shaped by the interaction of keratinocytes with many different cell types (innate and adaptive immune cells, vasculature) spanning the dermal layer of the skin. The pathogenesis of psoriasis can be conceptualized into an initiation phase possibly triggered by trauma (Koebner phenomenon), infection, or drugs and a maintenance phase characterized by a chronic clinical progression.

• #4

  https://link.springer.com/article/10.1007/s12016-024-08991-7

  Psoriasis is one of the most common inflammatory skin diseases with a chronic, relapsing-remitting course. The last decades of intense research uncovered a pathological network of interactions between immune cells and other types of cells in the pathogenesis of psoriasis. Emerging evidence indicates that dendritic cells, TH17 cells, and keratinocytes constitute a pathogenic triad in psoriasis. Dendritic cells produce TNF- and IL-23 to promote T cell differentiation toward TH17 cells that produce key psoriatic cytokines IL-17, IFN-, and IL-22. Their activity results in skin inflammation and activation and hyperproliferation of keratinocytes. […] In addition, other cells and signaling pathways are implicated in the pathogenesis of psoriasis, including TH9 cells, TH22 cells, CD8+ cytotoxic cells, neutrophils, T cells, and cytokines and chemokines secreted by them. New insights from high-throughput analysis of lesional skin identified novel signaling pathways and cell populations involved in the pathogenesis. These studies not only expanded our knowledge about the mechanisms of immune response and the pathogenesis of psoriasis but also resulted in a revolution in the clinical management of patients with psoriasis. Thus, understanding the mechanisms of immune response in psoriatic inflammation is crucial for further studies, the development of novel therapeutic strategies, and the clinical management of psoriasis patients. The aim of the review was to comprehensively present the dysregulation of immune response in psoriasis with an emphasis on recent findings. Here, we described the role of immune cells, including T cells, B cells, dendritic cells, neutrophils, monocytes, mast cells, and innate lymphoid cells (ILCs), as well as non-immune cells, including keratinocytes, fibroblasts, endothelial cells, and platelets in the initiation, development, and progression of psoriasis.

• #5 Psoriasis Pathogenesis and Treatment

  https://www.mdpi.com/1422-0067/20/6/1475

  Disturbances in the innate and adaptive cutaneous immune responses are responsible for the development and sustainment of psoriatic inflammation. An activation of the innate immune system driven by endogenous danger signals and cytokines characteristically coexists with an autoinflammatory perpetuation in some patients, and T cell-driven autoimmune reactions in others. Thus, psoriasis shows traits of an autoimmune disease on an (auto)inflammatory background, with both mechanisms overlapping and even potentiating one another. […] The main clinical findings in psoriasis are evident at the outermost layer of the skin, which is made up of keratinocytes. However, the development of the psoriatic plaque is not restricted to inflammation in the epidermal layer, but rather is shaped by the interaction of keratinocytes with many different cell types (innate and adaptive immune cells, vasculature) spanning the dermal layer of the skin. The pathogenesis of psoriasis can be conceptualized into an initiation phase possibly triggered by trauma (Koebner phenomenon), infection, or drugs and a maintenance phase characterized by a chronic clinical progression.

• #6

  https://link.springer.com/article/10.1007/s12016-024-08991-7

  Psoriasis is characterized by the dysregulation of the cytokine network with multiple self-amplifying feeds accelerating pathogenic circuits. Psoriatic inflammation can be triggered in predisposed individuals by mechanical stress (Koebner phenomenon), air pollutants, sun exposure, drugs, infections, or vaccination. It seems that pattern recognition receptors (PRRs), especially Toll-like receptors (TLRs), are crucial mediators of the response to these triggering factors. […] The first studies suggested that psoriasis is a classical TH1 inflammatory disease with IFN- as a key mediator of psoriatic inflammation. Further intense studies revealed that it is associated with not only overactivated TH1 response but also TH17 and TH22 responses. In general, proinflammatory cytokines and factors stimulating proliferation in psoriasis are produced mainly by T cells (IL-17, IL-21, IL-22, IFN-), DCs (TNF-, IL-6, IL-20, IL-23, NO), and KCs (antimicrobial peptides (AMPs), IL-20, chemokines). These cells form a key pathogenic loop in psoriasis that involves a triad of IL-23-producing DCs, IL-17-producing TH17, and activated KCs.

• #7 Psoriasis Pathogenesis and Treatment

  https://www.mdpi.com/1422-0067/20/6/1475

  It is well known that dendritic cells play a major role in the initial stages of disease. Dendritic cells are professional antigen-presenting cells. However, their activation in psoriasis is not entirely clear. One of the proposed mechanisms involves the recognition of antimicrobial peptides (AMPs), which are secreted by keratinocytes in response to injury and are characteristically overexpressed in psoriatic skin. […] The activation of the adaptive immune response via the distinct T cell subsets drives the maintenance phase of psoriatic inflammation. Th17 cytokines, namely IL-17, IL-21, and IL-22 activate keratinocyte proliferation in the epidermis. […] The TNFα–IL-23–Th17 inflammatory pathway characterizes plaque-type psoriasis. The IL-17 cytokine family is composed of six members: IL-17A–F. They are produced by different cell types, and are important regulators of inflammatory responses.

• #8 Advances in the pathogenesis of psoriasis: from keratinocyte perspective | Cell Death & Disease

  https://www.nature.com/articles/s41419-022-04523-3

  Emerging evidence has shown that keratinocytes could act as a trigger in psoriasis, and would be a promising target for psoriasis treatment. […] Keratinocytes play essential roles in both the initiation and maintenance phases of psoriasis. […] Stressed keratinocytes release self-nucleotides and antimicrobial peptides, thus promoting the activation of pDCs. […] Once activated by proinflammatory cytokines synergistically, keratinocytes are highly proliferative and can produce copious chemokines (e.g. CXCL1/2/3, CXCL8, CXCL9/10/11, CCL2, and CCL20) to recruit leukocytes (such as neutrophils, Th17 cells, dendritic cells, and macrophages), antimicrobial peptides (e.g. S100A7/8/9/12, hBD2, and LL37) to induce innate immunity, and other inflammatory mediators to amplify inflammation. […] The crosstalk between keratinocytes and immune cells especially Th17 cells results in the induction and maintenance of psoriasis with hyperproliferation and aberrant differentiation of keratinocytes, dilated and hyperplastic blood vessels, and infiltration of inflammatory cells like leukocytes.

• #9 Psoriasis: From Pathogenesis to Pharmacological and Nano-Technological-Based Therapeutics

  https://www.mdpi.com/1422-0067/22/9/4983

  LL-37 has been recognised as a participant in the pathogenesis of the psoriasis, due to the boundaries with DNA-stimulating toll-like receptor 9 in plasmacytoid dendritic cells. […] The maintenance phase of psoriatic inflammation is driven by the activation of the adaptative immune response via the T cell subsets. […] The proliferation of keratinocytes in epidermis is engaged by two different vias, inflammation by action of TNF- α, IL-17 and IFN- γ, and LL-37 complexed with DNA, resulting in an increasing production of type I IFNs. […] All these mediators further maintain keratinocytes activation, producing LL-37, proinflammatory cytokines (TNF-α, IL-1β, IL-6), chemokines, and S100 proteins, propagating the chronic inflammation. […] Plaque-type psoriasis is characterised by the inflammatory pathway TNFα–IL-23–Th17.

• #10 Psoriasis: Unraveling Disease Mechanisms and Advancing Pharmacological | JIR

  https://www.dovepress.com/psoriasis-unraveling-disease-mechanisms-and-advancing-pharmacological–peer-reviewed-fulltext-article-JIR

  LL-37 induces type I interferon production, promoting dendritic cell maturation and driving Th1 and Th17 differentiation. […] Elevated RORC mRNA in psoriatic patients supports the involvement of Th17 cells in disease pathogenesis. […] Targeting RORt with small molecule inhibitors offers a potential therapeutic strategy to suppress the proinflammatory IL-17/IL-23 axis. […] The IL-23/Th17 axis has emerged as a key pathogenic pathway. […] IL-23, produced by antigen-presenting cells like dendritic cells, activates Th17 cells that subsequently secrete IL-17. […] This cytokine not only promotes keratinocyte proliferation and activation but also amplifies the inflammatory response by inducing the release of other pro-inflammatory cytokines, such as IL-6 and TNF. […] The feedforward loop created by IL-17 induces a vicious cycle of continuous inflammation, which leads to the hallmark symptoms of psoriasis, including thickened, scaly plaques.

• #11 Psoriasis Pathogenesis and Treatment

  https://www.mdpi.com/1422-0067/20/6/1475

  It is well known that dendritic cells play a major role in the initial stages of disease. Dendritic cells are professional antigen-presenting cells. However, their activation in psoriasis is not entirely clear. One of the proposed mechanisms involves the recognition of antimicrobial peptides (AMPs), which are secreted by keratinocytes in response to injury and are characteristically overexpressed in psoriatic skin. […] The activation of the adaptive immune response via the distinct T cell subsets drives the maintenance phase of psoriatic inflammation. Th17 cytokines, namely IL-17, IL-21, and IL-22 activate keratinocyte proliferation in the epidermis. […] The TNFα–IL-23–Th17 inflammatory pathway characterizes plaque-type psoriasis. The IL-17 cytokine family is composed of six members: IL-17A–F. They are produced by different cell types, and are important regulators of inflammatory responses.

• #12

  https://link.springer.com/article/10.1007/s12016-024-08991-7

  Psoriasis is characterized by the dysregulation of the cytokine network with multiple self-amplifying feeds accelerating pathogenic circuits. Psoriatic inflammation can be triggered in predisposed individuals by mechanical stress (Koebner phenomenon), air pollutants, sun exposure, drugs, infections, or vaccination. It seems that pattern recognition receptors (PRRs), especially Toll-like receptors (TLRs), are crucial mediators of the response to these triggering factors. […] The first studies suggested that psoriasis is a classical TH1 inflammatory disease with IFN- as a key mediator of psoriatic inflammation. Further intense studies revealed that it is associated with not only overactivated TH1 response but also TH17 and TH22 responses. In general, proinflammatory cytokines and factors stimulating proliferation in psoriasis are produced mainly by T cells (IL-17, IL-21, IL-22, IFN-), DCs (TNF-, IL-6, IL-20, IL-23, NO), and KCs (antimicrobial peptides (AMPs), IL-20, chemokines). These cells form a key pathogenic loop in psoriasis that involves a triad of IL-23-producing DCs, IL-17-producing TH17, and activated KCs.

• #13 Psoriasis Pathogenesis and Treatment

  https://www.mdpi.com/1422-0067/20/6/1475

  It is well known that dendritic cells play a major role in the initial stages of disease. Dendritic cells are professional antigen-presenting cells. However, their activation in psoriasis is not entirely clear. One of the proposed mechanisms involves the recognition of antimicrobial peptides (AMPs), which are secreted by keratinocytes in response to injury and are characteristically overexpressed in psoriatic skin. […] The activation of the adaptive immune response via the distinct T cell subsets drives the maintenance phase of psoriatic inflammation. Th17 cytokines, namely IL-17, IL-21, and IL-22 activate keratinocyte proliferation in the epidermis. […] The TNFα–IL-23–Th17 inflammatory pathway characterizes plaque-type psoriasis. The IL-17 cytokine family is composed of six members: IL-17A–F. They are produced by different cell types, and are important regulators of inflammatory responses.

• #14

  https://link.springer.com/article/10.1007/s12016-024-08991-7

  Dysregulation of the cytokine profile is associated with overactivation of type 1, type 17, and type 22 pathways as well as innate inflammatory pathways. TNF- is the founder cytokine that initiates downstream inflammatory signaling in psoriasis. There are multiple triggers of TNF- secretion, including skin injury, environmental stimuli, autoantigens, and TLRs agonists. In psoriatic skin, it is produced predominantly by activated T cells and antigen-presenting cells (APCs), including dermal DCs. TNF- synergizes with IFN- to induce the expression of chemokines and inflammatory adhesion molecules by endothelial cells which promote the infiltration of immune cells, especially T cells, into the skin. […] IL-23 is a heterodimer of p19 and p40 subunits. It is a key regulator of the type 17 pathway activating a variety of cells, including TH17, Tc17, T cells, and innate lymphoid cells type 3 (ILC3) to produce IL-17. Moreover, IL-23 is a key cytokine that regulates the survival and pathogenic potential of TH17 cells.

• #15

  https://link.springer.com/article/10.1007/s12016-024-08991-7

  TH17 cells orchestrate inflammation via multiple cytokines, especially IL-17. This cytokine regulates immune response to different pathogens and tissue repair processes. However, IL-17 is also implicated in a variety of TH17-mediated inflammatory autoimmune diseases. In lesional skin, the level of IL-17 family members, especially IL-17A, IL-17C, and IL-17F, is potently upregulated. […] IL-17 exerts a variety of effects in inflamed psoriatic skin, including activation of KCs to produce AMPs, upregulation of ICAM-1 in endothelial cells to promote tissue inflammation and promotion of the infiltration of immune cells. Moreover, IL-17 potentiates inflammation by the induction of multiple pro-inflammatory cytokines and chemokines. IL-17 synergizes with TNF- to induce hyperproliferation of KCs, TH17-polarized inflammation, and upregulate psoriasis-related genes.

• #16 Signaling pathways and targeted therapies for psoriasis | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-023-01655-6

  Psoriasis is a common, chronic, and inflammatory skin disease with a high burden on individuals, health systems, and society worldwide. With the immunological pathologies and pathogenesis of psoriasis becoming gradually revealed, the therapeutic approaches for this disease have gained revolutionary progress. Nevertheless, the mechanisms of less common forms of psoriasis remain elusive. […] Therefore, it is crucial to have a comprehensive understanding of the mechanisms behind psoriasis pathogenesis, which might offer new insights for research and lead to more substantive progress in therapeutic approaches and expand clinical options for psoriasis treatment. […] The pathogenesis of psoriasis has gradually been elucidated in the past years. Studies have revealed that psoriasis is regulated by the complex interactions between extracellular cytokine pathways and intracellular signaling molecules. A variety of cytokines transmit extracellular signals to the cell membrane and then are recognized by related receptors, leading to the activation of intracellular signaling pathways and inducing a series of events that ultimately result in the inflammatory signaling cascade. Epigenetics also plays a critical role in the pathogenesis of the psoriasis. Furthermore, recent studies also suggested that metabolic reprogramming is emerging as another crucial regulatory paradigm for psoriasis.

• #17 Signaling pathways and targeted therapies for psoriasis | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-023-01655-6

  The IL-17 family includes six structurally related cytokines: IL-17A to IL-17F. Among them, it is reported that IL-17A, IL-17C, and IL-17F are related to the pathogenesis of psoriasis due to their increased expression in psoriatic lesions. The released IL-17, especially IL-17A and IL-17F, mainly acts directly on keratinocytes to stimulate the production of some molecules such as cytokines, antimicrobial peptides (AMPs), and -defensins, as well as chemokines, including chemokine (C-X-C motif) ligand 1 (CXCL1), CXCL2, CXCL8, and CCL20; these molecules are often increased in psoriatic lesions to attract neutrophils, macrophages and lymphocytes. […] Tumor necrosis factor (TNF)- is another critical inflammatory cytokine that is highly expressed in psoriatic lesions. This cytokine plays a pivotal role in the pathogenesis of psoriasis, which is also demonstrated by the efficacy of TNF–targeted therapies. TNF- is produced by a variety of cells related to the development of psoriasis, such as keratinocytes, DCs, neutrophils, mast cells, as well as NKT, Th1, Th17 and Th22 cells. It acts on the targeted cells mainly via two types of TNF receptors, i.e., TNFRI (p55) and TNF-RII (p75).

• #18 Signaling pathways and targeted therapies for psoriasis | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-023-01655-6

  The IL-17 family includes six structurally related cytokines: IL-17A to IL-17F. Among them, it is reported that IL-17A, IL-17C, and IL-17F are related to the pathogenesis of psoriasis due to their increased expression in psoriatic lesions. The released IL-17, especially IL-17A and IL-17F, mainly acts directly on keratinocytes to stimulate the production of some molecules such as cytokines, antimicrobial peptides (AMPs), and -defensins, as well as chemokines, including chemokine (C-X-C motif) ligand 1 (CXCL1), CXCL2, CXCL8, and CCL20; these molecules are often increased in psoriatic lesions to attract neutrophils, macrophages and lymphocytes. […] Tumor necrosis factor (TNF)- is another critical inflammatory cytokine that is highly expressed in psoriatic lesions. This cytokine plays a pivotal role in the pathogenesis of psoriasis, which is also demonstrated by the efficacy of TNF–targeted therapies. TNF- is produced by a variety of cells related to the development of psoriasis, such as keratinocytes, DCs, neutrophils, mast cells, as well as NKT, Th1, Th17 and Th22 cells. It acts on the targeted cells mainly via two types of TNF receptors, i.e., TNFRI (p55) and TNF-RII (p75).

• #19 Signaling pathways and targeted therapies for psoriasis | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-023-01655-6

  The IL-17 family includes six structurally related cytokines: IL-17A to IL-17F. Among them, it is reported that IL-17A, IL-17C, and IL-17F are related to the pathogenesis of psoriasis due to their increased expression in psoriatic lesions. The released IL-17, especially IL-17A and IL-17F, mainly acts directly on keratinocytes to stimulate the production of some molecules such as cytokines, antimicrobial peptides (AMPs), and -defensins, as well as chemokines, including chemokine (C-X-C motif) ligand 1 (CXCL1), CXCL2, CXCL8, and CCL20; these molecules are often increased in psoriatic lesions to attract neutrophils, macrophages and lymphocytes. […] Tumor necrosis factor (TNF)- is another critical inflammatory cytokine that is highly expressed in psoriatic lesions. This cytokine plays a pivotal role in the pathogenesis of psoriasis, which is also demonstrated by the efficacy of TNF–targeted therapies. TNF- is produced by a variety of cells related to the development of psoriasis, such as keratinocytes, DCs, neutrophils, mast cells, as well as NKT, Th1, Th17 and Th22 cells. It acts on the targeted cells mainly via two types of TNF receptors, i.e., TNFRI (p55) and TNF-RII (p75).

• #20 Advances in the pathogenesis of psoriasis: from keratinocyte perspective | Cell Death & Disease

  https://www.nature.com/articles/s41419-022-04523-3

  Keratinocytes are critical in psoriasis pathogenesis and participate in both the initiation and maintenance phases of psoriasis. […] Various factors such as genetics, cytokines and receptors, metabolism, cell signaling, transcription factors, non-coding RNAs, antimicrobial peptides, etc. modulate the functions of keratinocytes and influence psoriasis. […] Targeting those factors provides promising therapeutic strategies for psoriasis. […] The pathogenesis of psoriasis is complicated, which involves the interplay between keratinocytes, immune cells, and other skin-resident cells. Over the last 2 decades, psoriasis has been considered as an immune cell-driven disease, and keratinocytes are just executors to perform the function of immune cells during psoriasis. […] Activation of plasmacytoid dendritic (pDCs) promotes myeloid dendritic cells (mDCs) maturation and production of TNF-, IL-12, and IL-23, which leads to the activation of Th (T helper) 1 and Th17 and subsequent secretion of inflammatory cytokines, such as TNF-, IL-17, IL-21, and IL-22. Keratinocytes are then activated by these cytokines (especially IL-17) and produce antimicrobial peptides, cytokines, and chemokines, contributing to the amplification of inflammation.

• #21 Psoriasis Immunopathogenesis

  https://www.heraldopenaccess.us/openaccess/psoriasis-immunopathogenesis

  The autoimmune process in psoriasis is deemed one of the major mechanisms of disease development. It is expected that keratinocytes are trigger cells. In the event of a damage (trauma, infections, drugs, UV), they „supply” autoimmune antigens and activate antigen-presenting cells due to the secretion of a large set of congenital immunity factors (cytokines, chemokines, antimicrobial peptides). […] The key moment in the autoimmune inflammation initiation is the immune tolerance failure which is currently associated with the activity of cytosolic and extracellular DNA. […] Psoriasis is a chronic immune-related dermatosis, and the formation of a T cell immune response that develops autoimmune inflammation plays the main role in its pathogenesis. The preservation of memory T cells after psoriasis onset is the formation of the disease’s immunological memory; they explain its incurability and relapsing course.

• #22 The Role of Oxidative Stress in the Induction and Development of Psoriasis

  https://www.imrpress.com/journal/FBL/28/6/10.31083/j.fbl2806118/htm

  Keratinocytes play a direct role in the intensification and subsequent development of the chronic phase of inflammation. As a result of exposure to pro-inflammatory cytokines, keratinocytes, in addition to high proliferative activity, acquire the ability to produce high levels of cytokines, such as: CXCL1/2/3, CXCL8, CCL2 and CCL20, which lead to increased recruitment of leukocytes involved in autoimmune inflammation, including: dendritic cells, macrophages, neutrophils, and Th17 lymphocytes. Keratinocytes produce new portions of ROS, which act as strong chemoattractants for neutrophils, promoting their invasion and accumulation in skin psoriatic lesions. Neutrophils, like other immune cells in the inflammatory focus, in turn release high levels of ROS, which lead to an even greater increase in OS and the development of the chain reaction of increased inflammation, which eventually develops into a state of chronic inflammation.

• #23 Psoriasis Immunopathogenesis

  https://www.heraldopenaccess.us/openaccess/psoriasis-immunopathogenesis

  The autoimmune process in psoriasis is deemed one of the major mechanisms of disease development. It is expected that keratinocytes are trigger cells. In the event of a damage (trauma, infections, drugs, UV), they „supply” autoimmune antigens and activate antigen-presenting cells due to the secretion of a large set of congenital immunity factors (cytokines, chemokines, antimicrobial peptides). […] The key moment in the autoimmune inflammation initiation is the immune tolerance failure which is currently associated with the activity of cytosolic and extracellular DNA. […] Psoriasis is a chronic immune-related dermatosis, and the formation of a T cell immune response that develops autoimmune inflammation plays the main role in its pathogenesis. The preservation of memory T cells after psoriasis onset is the formation of the disease’s immunological memory; they explain its incurability and relapsing course.

• #24

  https://link.springer.com/article/10.1007/s12016-024-08991-7

  In psoriasis, T cells infiltrating lesional skin have substantially upregulated expression of chemokine receptors, including a skin-homing receptor, CCR4, and CCR6. Moreover, there is an increased fraction of CCR4+ and CCR6+ T cells in peripheral blood. Due to increased expression of chemokine receptors, skin-homing T cells of psoriasis patients respond to lower concentrations of chemokines, including CCL20, and exhibit stronger chemotactic responses compared to T cells of healthy individuals. […] Multiple types of immune cells regulate the initiation, maintenance, and progression of psoriatic inflammation. T cells, especially TH17 cells, together with DCs are the main players in the pathogenesis of psoriasis. Nonetheless, a variety of other types of immune cells, including neutrophils, monocytes, macrophages, mast cells, and ILCs participate in the pathogenesis of psoriasis. In general, innate immune cells, especially neutrophils, are key cells in the early phases of psoriasis development while T cell-dominated adaptive inflammation is a feature of stable plaques in the later phases.

• #25

  https://link.springer.com/article/10.1007/s12016-024-08991-7

  In psoriasis, T cells infiltrating lesional skin have substantially upregulated expression of chemokine receptors, including a skin-homing receptor, CCR4, and CCR6. Moreover, there is an increased fraction of CCR4+ and CCR6+ T cells in peripheral blood. Due to increased expression of chemokine receptors, skin-homing T cells of psoriasis patients respond to lower concentrations of chemokines, including CCL20, and exhibit stronger chemotactic responses compared to T cells of healthy individuals. […] Multiple types of immune cells regulate the initiation, maintenance, and progression of psoriatic inflammation. T cells, especially TH17 cells, together with DCs are the main players in the pathogenesis of psoriasis. Nonetheless, a variety of other types of immune cells, including neutrophils, monocytes, macrophages, mast cells, and ILCs participate in the pathogenesis of psoriasis. In general, innate immune cells, especially neutrophils, are key cells in the early phases of psoriasis development while T cell-dominated adaptive inflammation is a feature of stable plaques in the later phases.

• #26

  https://link.springer.com/article/10.1007/s12016-024-08991-7

  Neutrophils participate in the initiation of the disease and early phases of progression of psoriatic inflammation. Early lesions and prepsoriatic skin adjacent to active lesions are characterized by the potent infiltration of CD15+ neutrophils. Chronic lesions are also infiltrated by neutrophils, especially CD15posCD10pos and CD15posCD10neg neutrophils. Neutrophils are also enriched in the peripheral blood of psoriatic patients and are in a pre-activated state. […] In psoriatic lesions, IL-17+ neutrophils together with IL-17+ mast cells are found in higher densities than IL-17+ T cells. It seems that neutrophils do not express IL-17A, but can accumulate it and release it during the formation of neutrophil extracellular traps (NETs). […] DCs are a major type of leukocytes in psoriatic lesions with numbers exceeding the number of T cells. The main role of DCs in psoriasis is to orchestrate the immune response of T cells. Psoriatic DCs strongly induce both TH17 and TH1 T cells.

• #27

  https://link.springer.com/article/10.1007/s12016-024-08991-7

  Neutrophils participate in the initiation of the disease and early phases of progression of psoriatic inflammation. Early lesions and prepsoriatic skin adjacent to active lesions are characterized by the potent infiltration of CD15+ neutrophils. Chronic lesions are also infiltrated by neutrophils, especially CD15posCD10pos and CD15posCD10neg neutrophils. Neutrophils are also enriched in the peripheral blood of psoriatic patients and are in a pre-activated state. […] In psoriatic lesions, IL-17+ neutrophils together with IL-17+ mast cells are found in higher densities than IL-17+ T cells. It seems that neutrophils do not express IL-17A, but can accumulate it and release it during the formation of neutrophil extracellular traps (NETs). […] DCs are a major type of leukocytes in psoriatic lesions with numbers exceeding the number of T cells. The main role of DCs in psoriasis is to orchestrate the immune response of T cells. Psoriatic DCs strongly induce both TH17 and TH1 T cells.

• #28 Psoriasis Pathogenesis and Treatment

  https://www.mdpi.com/1422-0067/20/6/1475

  Despite solid evidence of genetic relevance in the pathogenesis of psoriasis, no single genetic variant seems to be sufficient to account on its own for the development of disease. Hence, a multifactorial setting including multiple genetic mutations and environmental factors, which have been attributed up to 30% of disease risk, ought to be considered. […] The quest for the missing heritability associated with psoriasis candidate genes has fueled the search for epigenetic modifications. Epigenetic mechanisms modify gene expression without changing the genomic sequence; some examples include: long noncoding RNA (lncRNA), microRNA (miRNA) silencing, and cytosine and guanine (CpG) methylation. […] The skin microbiome exerts an active role in immune regulation and pathogen defense by stimulating the production of antibacterial peptides and through biofilm formation. A differential colonizing microbiota in comparison to healthy skin has been found in several dermatologic diseases, including atopic dermatitis, psoriasis, and acne vulgaris.

• #29 Psoriasis Pathogenesis and Treatment

  https://www.mdpi.com/1422-0067/20/6/1475

  Despite solid evidence of genetic relevance in the pathogenesis of psoriasis, no single genetic variant seems to be sufficient to account on its own for the development of disease. Hence, a multifactorial setting including multiple genetic mutations and environmental factors, which have been attributed up to 30% of disease risk, ought to be considered. […] The quest for the missing heritability associated with psoriasis candidate genes has fueled the search for epigenetic modifications. Epigenetic mechanisms modify gene expression without changing the genomic sequence; some examples include: long noncoding RNA (lncRNA), microRNA (miRNA) silencing, and cytosine and guanine (CpG) methylation. […] The skin microbiome exerts an active role in immune regulation and pathogen defense by stimulating the production of antibacterial peptides and through biofilm formation. A differential colonizing microbiota in comparison to healthy skin has been found in several dermatologic diseases, including atopic dermatitis, psoriasis, and acne vulgaris.

• #30 Psoriasis Pathogenesis and Treatment

  https://www.mdpi.com/1422-0067/20/6/1475

• #31 Triggers for the onset and recurrence of psoriasis: a review and update | Cell Communication and Signaling | Full Text

  https://biosignaling.biomedcentral.com/articles/10.1186/s12964-023-01381-0

  The alteration of gut microbiota in both composition and functional potentials was confirmed in patients with psoriasis compared to healthy controls. […] The dysbiosis of gut microbiota may increase intestinal permeability, also called leaky gut, by reducing the thickness of the mucus layers, disturbing the proliferation and metabolism of intestinal epithelial cells, and affecting the production of AMPs. […] The microbiota can modify immune activity through microbial metabolites in the gut. […] The treatment of probiotics has demonstrated potential benefits in the improvement of psoriasis, though no standardized treatment has been formulated. […] Dysregulated lipid metabolism is involved in the pathogenesis of psoriasis. […] Various psoriasis RNA-seq datasets have shown that lipid metabolism pathways are deeply involved in the pathogenesis of psoriasis.

• #32 Advances in the pathogenesis of psoriasis: from keratinocyte perspective | Cell Death & Disease

  https://www.nature.com/articles/s41419-022-04523-3

  The IL-23/IL-17 cytokine axis is considered as a major driver of psoriasis. […] IL-17A, the major downstream cytokine of IL-23, is most strongly implicated and well-studied in psoriasis pathogenesis. […] Briefly, IL-17A binds to its receptors on keratinocytes, through multiple cell signaling pathways, it induces the production of keratinocyte-derived antimicrobial peptides (e.g. S100A7, LL37, and DEFB4A) to activate innate immunity, chemokines (e.g. CXCL1, CXCL8, and CCL20) to recruit leukocytes such as neutrophils, Th17 cells, mDCs and macrophage, and multiple pro-inflammatory genes (such as IL-1, IL-6, IL-8, and TNF-), thus amplifying the IL-23/IL-17A axis and producing the feed forward inflammatory circuits. […] However, IL-17A could indirectly induce epidermal hyperplasia via increased expression of IL-19 and IL-36 by keratinocytes.

• #33 Advances in the pathogenesis of psoriasis: from keratinocyte perspective | Cell Death & Disease

  https://www.nature.com/articles/s41419-022-04523-3

  The IL-23/IL-17 cytokine axis is considered as a major driver of psoriasis. […] IL-17A, the major downstream cytokine of IL-23, is most strongly implicated and well-studied in psoriasis pathogenesis. […] Briefly, IL-17A binds to its receptors on keratinocytes, through multiple cell signaling pathways, it induces the production of keratinocyte-derived antimicrobial peptides (e.g. S100A7, LL37, and DEFB4A) to activate innate immunity, chemokines (e.g. CXCL1, CXCL8, and CCL20) to recruit leukocytes such as neutrophils, Th17 cells, mDCs and macrophage, and multiple pro-inflammatory genes (such as IL-1, IL-6, IL-8, and TNF-), thus amplifying the IL-23/IL-17A axis and producing the feed forward inflammatory circuits. […] However, IL-17A could indirectly induce epidermal hyperplasia via increased expression of IL-19 and IL-36 by keratinocytes.

• #34 Advances in the pathogenesis of psoriasis: from keratinocyte perspective | Cell Death & Disease

  https://www.nature.com/articles/s41419-022-04523-3

  The IL-36 family cytokines are emerging as crucial players in the pathogenesis of psoriasis. […] Notably, IL-36 exerts its pathogenic role by promoting keratinocyte proliferation and enhancing the production of inflammatory cytokines and chemokines to amplify psoriatic inflammation. […] In this review, we have highlighted the critical roles of keratinocytes in psoriasis. Keratinocytes participate in both the initiation and maintenance phases of psoriasis. There are various factors that can regulate keratinocytes, including genetic regulation, cytokines and receptors, metabolism, cell signaling, transcription factors, non-coding RNAs, antimicrobial peptides, and proteins with other different functions. These modulating factors are not independent, but work together to alter the biological behavior of keratinocytes via multiple mechanisms, linking keratinocytes with psoriasis.

• #35 Advances in the pathogenesis of psoriasis: from keratinocyte perspective | Cell Death & Disease

  https://www.nature.com/articles/s41419-022-04523-3

  The IL-36 family cytokines are emerging as crucial players in the pathogenesis of psoriasis. […] Notably, IL-36 exerts its pathogenic role by promoting keratinocyte proliferation and enhancing the production of inflammatory cytokines and chemokines to amplify psoriatic inflammation. […] In this review, we have highlighted the critical roles of keratinocytes in psoriasis. Keratinocytes participate in both the initiation and maintenance phases of psoriasis. There are various factors that can regulate keratinocytes, including genetic regulation, cytokines and receptors, metabolism, cell signaling, transcription factors, non-coding RNAs, antimicrobial peptides, and proteins with other different functions. These modulating factors are not independent, but work together to alter the biological behavior of keratinocytes via multiple mechanisms, linking keratinocytes with psoriasis.

• #36 The Role of Oxidative Stress in the Induction and Development of Psoriasis

  https://www.imrpress.com/journal/FBL/28/6/10.31083/j.fbl2806118/htm

  OS occurs as a result of an imbalance between the production of ROS and the functioning of the antioxidant system. The development of OS in keratinocytes affects the triggering of the inflammatory response through the impact on several signaling pathways, such as: NF-κB, MAPK and STAT3, which leads to the production of pro-inflammatory cytokines. The main symptom of autoimmune diseases, including psoriasis, is the destruction of the organism’s own intact tissues by the immune system as a result of impaired antigen recognition, during which autoantigens are recognized as foreign. Under conditions of increased OS, keratinocytes begin to secrete proteins into the extracellular space, which are recognized by immune cells as autoantigens. OS also contributes at this stage of psoriasis pathogenesis, since ROS are stimulators of antigen presentation by dendritic cells. The imbalance of redox condition in psoriasis is observed systemically, and not only in keratinocytes, which provides additional stimulation to the immune system, primarily by increasing the production of pro-inflammatory cytokines. Thus, through the production of TNF-α and IFNγ by dendritic cells, ROS initiate the proliferation and differentiation of T-helpers, the main populations of which in psoriasis are Th17, Th1 and Th22, which in turn produce such pro-inflammatory cytokines as: IL-17, IL -23, TNF-α, IL-22, IL-26 and IL-29. The pro-inflammatory cytokines contribute to increased proliferation of keratinocytes, which leads to the development of epidermal hyperplasia, which is one of the significant manifestations in patients with psoriasis.

• #37 The Role of Oxidative Stress in the Induction and Development of Psoriasis

  https://www.imrpress.com/journal/FBL/28/6/10.31083/j.fbl2806118/htm

  OS occurs as a result of an imbalance between the production of ROS and the functioning of the antioxidant system. The development of OS in keratinocytes affects the triggering of the inflammatory response through the impact on several signaling pathways, such as: NF-κB, MAPK and STAT3, which leads to the production of pro-inflammatory cytokines. The main symptom of autoimmune diseases, including psoriasis, is the destruction of the organism’s own intact tissues by the immune system as a result of impaired antigen recognition, during which autoantigens are recognized as foreign. Under conditions of increased OS, keratinocytes begin to secrete proteins into the extracellular space, which are recognized by immune cells as autoantigens. OS also contributes at this stage of psoriasis pathogenesis, since ROS are stimulators of antigen presentation by dendritic cells. The imbalance of redox condition in psoriasis is observed systemically, and not only in keratinocytes, which provides additional stimulation to the immune system, primarily by increasing the production of pro-inflammatory cytokines. Thus, through the production of TNF-α and IFNγ by dendritic cells, ROS initiate the proliferation and differentiation of T-helpers, the main populations of which in psoriasis are Th17, Th1 and Th22, which in turn produce such pro-inflammatory cytokines as: IL-17, IL -23, TNF-α, IL-22, IL-26 and IL-29. The pro-inflammatory cytokines contribute to increased proliferation of keratinocytes, which leads to the development of epidermal hyperplasia, which is one of the significant manifestations in patients with psoriasis.

• #38 Review Outlines Role of Brain-Skin Connection in Psoriasis Pathogenesis

  https://www.ajmc.com/view/review-outlines-role-of-brainskin-connection-in-psoriasis-pathogenesis

  W niedawno opublikowanej recenzji badacze zbadali połączenie mózg-skóra oraz patogenezę łuszczycy, koncentrując się na systemie serotoninergicznym. […] Obecnie łuszczyca dotyka około 125 milionów ludzi na całym świecie, a jej patogeneza przypisywana jest kombinacji czynników genetycznych i środowiskowych. W szczególności interakcja między komórkami odpornościowymi wrodzonymi, komórkami odpornościowymi nabytymi a keratynocytami prowadzi do procesu zapalnego, który manifestuje się w skórze. […] Aby zrozumieć łuszczycę, niezbędne jest zrozumienie procesów leżących u podstaw odporności skóry i neuroendokrynologii, powiedzieli badacze. […] Połączenie mózg-skóra było szeroko badane, ponieważ skóra ma w pełni funkcjonalny obwodowy odpowiednik osi podwzgórze-przysadka-nadnercza (HPA). […] Ponadto udokumentowano, że serotonina działa jako mediator między skórą a systemem neuroendokrynnym. Serotonina przyczynia się również do efektów psychologicznego stresu na zakłócenie homeostazy skóry, a stres uznano za czynnik zaostrzający łuszczycę.

• #39 Review Outlines Role of Brain-Skin Connection in Psoriasis Pathogenesis

  https://www.ajmc.com/view/review-outlines-role-of-brainskin-connection-in-psoriasis-pathogenesis

  Nowe dowody sugerują, że oprócz modelu immunopatogenezy łuszczycy, inne składniki, takie jak neuropeptydy uwalniane przez skórny układ nerwowy i mikrobiom skóry, mogą również być mediatorami w tym procesie, powiedzieli badacze. […] Serotonina wspomaga proliferację komórek, regulację chemotaksji leukocytów, produkcję cytokin i aktywację komórek T, między innymi funkcjami. […] Receptory dla serotoniny to receptory 5-HT, które odgrywają ważną rolę w regulacji sygnalizacji immunologicznej. […] W skórze 5-HT bierze udział w zapaleniu i immunomodulacji i jest również głównym czynnikiem w depresji, która jest jednym z głównych współistniejących schorzeń łuszczycy. […] Badania wykazały, że transporter 5-HT jest inaczej wyrażany w skórze pacjentów z łuszczycą w porównaniu do zdrowej skóry. […] Połączenie mózg-skóra pomaga wyjaśnić, dlaczego stres psychologiczny może mieć wpływ na skórę, w tym rozwój lub zaostrzenie chorób skórnych, takich jak łuszczyca, atopowe zapalenie skóry i egzema, konkludują badacze.

• #40 Psoriasis Pathogenesis and Treatment

  https://www.mdpi.com/1422-0067/20/6/1475

  Drugs targeting TNFα, IL-23, and IL-17 and signaling pathways such as JAK/STAT are effective in the clinical management of plaque psoriasis. However, alternate inflammatory pathways may be valid for distinct psoriatic variants. […] Psoriasis shows clear autoimmune-related pathomechanisms. This very important area of research will allow for a deeper understanding of to which extent autoantigen-specific T cells contribute to the development, chronification, and overall course of the disease. […] The immunogenetics of IL-23 are strongly associated with psoriasis. IL-23 is a dimer composed of a specific subunit, p19, and a p40 subunit, which is shared with IL-12. IL-23 signals through a heterodimeric receptor expressed by both innate and adaptive immune cells, which include Th17, natural killer T, γδ T cells, and RORγt+ innate lymphoid cells.

• #41 Psoriasis Pathogenesis and Treatment

  https://www.mdpi.com/1422-0067/20/6/1475

  Drugs targeting TNFα, IL-23, and IL-17 and signaling pathways such as JAK/STAT are effective in the clinical management of plaque psoriasis. However, alternate inflammatory pathways may be valid for distinct psoriatic variants. […] Psoriasis shows clear autoimmune-related pathomechanisms. This very important area of research will allow for a deeper understanding of to which extent autoantigen-specific T cells contribute to the development, chronification, and overall course of the disease. […] The immunogenetics of IL-23 are strongly associated with psoriasis. IL-23 is a dimer composed of a specific subunit, p19, and a p40 subunit, which is shared with IL-12. IL-23 signals through a heterodimeric receptor expressed by both innate and adaptive immune cells, which include Th17, natural killer T, γδ T cells, and RORγt+ innate lymphoid cells.

• #42 Psoriasis Immunopathogenesis

  https://www.heraldopenaccess.us/openaccess/psoriasis-immunopathogenesis

  The introduction of an immunohistochemical study of the affected skin of psoriasis patients allowed scientists to determine the phenotype of the main immune cells involved in the inflammatory process. One of the dominant cell populations are T lymphocytes (CD3+), the number of which in the eruption areas increases by 6-10 times compared with healthy skin. […] Th17-lymphocytes are practically not found in healthy skin. The participation of these cells in the inflammatory process is associated with the autoimmune response development. Th17 are major figures in psoriasis pathogenesis, their participation in the inflammatory process gives it a specific character and leads to the development of clinical implications specifically attributed to psoriasis. […] The last scientific findings also point to the important role of Innate Lymphoid Cells (ILCs) in psoriasis pathogenesis.

• #43 Psoriasis Immunopathogenesis

  https://www.heraldopenaccess.us/openaccess/psoriasis-immunopathogenesis

  Thus, ILC3 can make a significant contribution to psoriasis pathogenesis by producing key anti-inflammatory IL-17 and IL-22 cytokines. Therefore, ILCs modulation is a new therapeutic approach to psoriasis patient management in the future. […] Psoriasis development mechanism during treatment with Genetically Engineered Biologic Drugs (GEBD) is not fully understood. […] The most possible is the hypothesis of the development of a disbalance between TNF- and INF- cytokines in patients who take genetically engineered biologic drugs. […] Since the last century, our visions of psoriasis pathogenesis have changed a lot. The concept of the immune system malfunctions has replaced the prevailing theory of the key role of a primary abnormality of keratinocyte differentiation. It is assumed that the balance change towards the increased synthesis of pro-inflammatory cytokines by immune-competent cells leads to the development of psoriatic manifestations in the skin.

• #44 IL-23 blockade with guselkumab potentially modifies psoriasis pathogenesis: rationale and study protocol of a phase 3b, randomised, double-blind, multicentre study in participants with moderate-to-severe plaque-type psoriasis (GUIDE) | BMJ Open

  https://bmjopen.bmj.com/content/11/9/e049822

  Here, we discuss the concept of modifying the disease course towards long-term remission as a potential novel treatment goal for psoriasis. […] Overall, current knowledge suggests that epidermal TRM generated by immune challenges in peripheral tissues persist in previously lesional psoriatic skin after healing. […] Recent findings suggest that IL-23 is involved in the differentiation and survival of pathogenic TRM. […] This immunological understanding of long-term drug-free remission would be a step towards disease modification, a principle that has been described for treatment of other autoimmune diseases (eg, RA and Crohns disease) with biological agents, but this is not yet clearly defined for psoriasis. […] Overall, preliminary clinical data suggest that early intervention with selective IL-23 inhibitors may have the potential to wield a profound effect in psoriasis that extends beyond short-term clearance of psoriatic skin lesions, and could instead lead to a long-term, sustained clinical response in certain patients.

• #45 IL-23 blockade with guselkumab potentially modifies psoriasis pathogenesis: rationale and study protocol of a phase 3b, randomised, double-blind, multicentre study in participants with moderate-to-severe plaque-type psoriasis (GUIDE) | BMJ Open

  https://bmjopen.bmj.com/content/11/9/e049822

  Here, we discuss the concept of modifying the disease course towards long-term remission as a potential novel treatment goal for psoriasis. […] Overall, current knowledge suggests that epidermal TRM generated by immune challenges in peripheral tissues persist in previously lesional psoriatic skin after healing. […] Recent findings suggest that IL-23 is involved in the differentiation and survival of pathogenic TRM. […] This immunological understanding of long-term drug-free remission would be a step towards disease modification, a principle that has been described for treatment of other autoimmune diseases (eg, RA and Crohns disease) with biological agents, but this is not yet clearly defined for psoriasis. […] Overall, preliminary clinical data suggest that early intervention with selective IL-23 inhibitors may have the potential to wield a profound effect in psoriasis that extends beyond short-term clearance of psoriatic skin lesions, and could instead lead to a long-term, sustained clinical response in certain patients.

• #46 IL-23 blockade with guselkumab potentially modifies psoriasis pathogenesis: rationale and study protocol of a phase 3b, randomised, double-blind, multicentre study in participants with moderate-to-severe plaque-type psoriasis (GUIDE) | BMJ Open

  https://bmjopen.bmj.com/content/11/9/e049822

  Here, we discuss the concept of modifying the disease course towards long-term remission as a potential novel treatment goal for psoriasis. […] Overall, current knowledge suggests that epidermal TRM generated by immune challenges in peripheral tissues persist in previously lesional psoriatic skin after healing. […] Recent findings suggest that IL-23 is involved in the differentiation and survival of pathogenic TRM. […] This immunological understanding of long-term drug-free remission would be a step towards disease modification, a principle that has been described for treatment of other autoimmune diseases (eg, RA and Crohns disease) with biological agents, but this is not yet clearly defined for psoriasis. […] Overall, preliminary clinical data suggest that early intervention with selective IL-23 inhibitors may have the potential to wield a profound effect in psoriasis that extends beyond short-term clearance of psoriatic skin lesions, and could instead lead to a long-term, sustained clinical response in certain patients.

• #47 Psoriasis Pathogenesis and Treatment

  https://www.mdpi.com/1422-0067/20/6/1475

  Drugs targeting TNFα, IL-23, and IL-17 and signaling pathways such as JAK/STAT are effective in the clinical management of plaque psoriasis. However, alternate inflammatory pathways may be valid for distinct psoriatic variants. […] Psoriasis shows clear autoimmune-related pathomechanisms. This very important area of research will allow for a deeper understanding of to which extent autoantigen-specific T cells contribute to the development, chronification, and overall course of the disease. […] The immunogenetics of IL-23 are strongly associated with psoriasis. IL-23 is a dimer composed of a specific subunit, p19, and a p40 subunit, which is shared with IL-12. IL-23 signals through a heterodimeric receptor expressed by both innate and adaptive immune cells, which include Th17, natural killer T, γδ T cells, and RORγt+ innate lymphoid cells.

• #48 Psoriasis Immunopathogenesis

  https://www.heraldopenaccess.us/openaccess/psoriasis-immunopathogenesis

  Thus, ILC3 can make a significant contribution to psoriasis pathogenesis by producing key anti-inflammatory IL-17 and IL-22 cytokines. Therefore, ILCs modulation is a new therapeutic approach to psoriasis patient management in the future. […] Psoriasis development mechanism during treatment with Genetically Engineered Biologic Drugs (GEBD) is not fully understood. […] The most possible is the hypothesis of the development of a disbalance between TNF- and INF- cytokines in patients who take genetically engineered biologic drugs. […] Since the last century, our visions of psoriasis pathogenesis have changed a lot. The concept of the immune system malfunctions has replaced the prevailing theory of the key role of a primary abnormality of keratinocyte differentiation. It is assumed that the balance change towards the increased synthesis of pro-inflammatory cytokines by immune-competent cells leads to the development of psoriatic manifestations in the skin.

• #49 Cellular mechanisms of psoriasis pathogenesis | CCID

  https://www.dovepress.com/cellular-mechanisms-of-psoriasis-pathogenesis-a-systemic-review-peer-reviewed-fulltext-article-CCID

  Psoriasis is a common inflammatory skin disease characterized by abnormal proliferation of epidermal keratinocytes and massive infiltration of inflammatory cells. Many kinds of cells, including keratinocytes, T lymphocytes, dendritic cells, neutrophils, and macrophages, are reported to play critical roles in the pathogenesis and progression of psoriasis. […] Psoriasis is characterized by hyperproliferation and abnormal differentiation of keratinocytes, and massive infiltration of inflammatory immune cells. […] Psoriasis is now considered to be caused by immune abnormalities, which are triggered by genetic and environmental factors. […] Keratinocytes, as well as a variety of immune cells, including T cells, plasmacytoid dendritic cells (pDCs), myeloid dendritic cells (mDCs), neutrophils, and macrophages, work together to form an inflammatory circuit to contribute to the pathogenesis and development of psoriasis.

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