Keratinocyte-Derived IL-17E Contributes to Inflammation in Psoriasis

Senra, Luisa; Stalder, Romaine; Martínez, David Álvarez; Chizzolini, Carlo; Boehncke, Wolf‐Henning; Brembilla, Nicolò Costantino

doi:10.1016/j.jid.2016.06.009

Cited by 78 publications

(88 citation statements)

References 55 publications

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“…As confirmed in many studies, psoriatic skin is characterized by high expression of IL-17A and IL-17F (31). More recently, other IL-17 family members, namely IL-17C and IL-17E, have been reported to be expressed in psoriatic skin (18). While IL-17A and IL-17F are mainly produced by immune cells (e.g., Th cells, γδ T cells), the cellular sources of IL-17E also include epithelial cells like keratinocytes.…”

Section: Organ-specific Pathophysiologymentioning

confidence: 64%

“…IL-17A and IL-17F are significantly implicated in immune responses to infectious pathogens and in the pathogenesis of inflammatory autoimmune diseases like psoriasis. Furthermore, evidence indicates an additional proinflammatory activity of IL-17C and IL-17E within the pathogenesis of psoriasis (18)(19)(20)(21).…”

Section: Biology Of Il-17a and Il-17fmentioning

confidence: 99%

“…1. As other IL-17s also play a pro-inflammatory role in psoriasis (17,18), the efficacy of brodalumab might be particularly high. Indeed, indirect comparisons point into this direction (63).…”

Section: Potential Therapeutic Implicationsmentioning

confidence: 99%

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IL-17A in Psoriasis and Beyond: Cardiovascular and Metabolic Implications

et al. 2020

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Interleukin 17A (IL-17A) is one of the currently known six members of the IL-17 cytokine family and is implicated in immune responses to infectious pathogens and in the pathogenesis of inflammatory autoimmune diseases like psoriasis. Psoriatic skin is characterized by high expression of IL-17A and IL-17F, which act on immune and non-immune cell types and strongly contribute to tissue inflammation. In psoriatic lesions, IL-17A, IL-17E, and IL-17F are involved in neutrophil accumulation, followed by the formation of epidermal micro abscesses. IL-17A together with other Th17 cytokines also upregulates the production of several chemokines that are implicated in psoriasis pathogenesis. IL17A-targeting antibodies show an impressive clinical efficacy in patients with psoriasis. Studies have reported an improvement of at least 75% as measured by the psoriasis area and severity index (PASI) in >80% of patients treated with anti-IL-17A therapy. Psoriasis skin manifestations, cardiovascular as well as metabolic disease in psoriasis appear to share pathogenic mechanisms evolving around IL-17A and its proinflammatory role. Thus, anti-IL-17A therapy not only improves skin manifestations of psoriasis, but also cardiovascular inflammation as well as metabolic factors and different domains of psoriatic arthritis (PsA) including peripheral arthritis, enthesitis, dactylitis, and axial involvement. This review summarizes the biological role of IL-17A, before reviewing currently available data on its role in the physiology and pathophysiology of the skin, as well as the cardiovascular and the metabolic system. In conclusion, clinical recommendations for patients with moderate to severe psoriasis based on the current available data are given.

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Section: Organ-specific Pathophysiologymentioning

confidence: 64%

Section: Biology Of Il-17a and Il-17fmentioning

confidence: 99%

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IL-17A in Psoriasis and Beyond: Cardiovascular and Metabolic Implications

et al. 2020

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“…IL-25 levels were increased in keratinocytes from inflamed skin of patients with contact dermatitis, as well as those with atopic dermatitis and psoriasis. 15,16 Based on studies using gene-deficient mice, T H 2 and T H 17 cytokines are thought to be involved in the development of CHS. 17,18 Therefore IL-25 might be involved in CHS induction by enhancing T H 2-type but suppressing T H 17-type immune responses.…”

mentioning

confidence: 99%

IL-25 enhances TH17 cell–mediated contact dermatitis by promoting IL-1β production by dermal dendritic cells

Suto

Nambu

Morita

et al. 2018

Journal of Allergy and Clinical Immunology

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“…Activated macrophages were also shown to produce inflammatory cytokines and chemokines attracting neutrophils. [ ] Lesional T cells induce keratinocyte proliferation and other hallmark features of psoriasis via release of several mediators, among which IL‐17A seems to be of particular importance. [ ] The clinical relevance namely of TNF‐α, IL‐17A and IL ‐ 23 is reflected by the high efficacy of antibodies blocking these cytokines in the treatment of psoriasis.…”

Section: Introductionmentioning

confidence: 99%

The Janus Kinase inhibitor tofacitinib impacts human dendritic cell differentiation and favours M1 macrophage development

Stalder

Zhang

Wrobel

et al. 2019

Experimental Dermatology

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Several cytokines signalling via Janus Kinase (JAK) proteins have been implicated in the pathogenesis of immune‐mediated inflammatory diseases, including psoriasis and rheumatoid arthritis (RA). Tofacitinib, a small JAK inhibitor, is approved for the treatment of RA and has demonstrated good efficacy in psoriasis phase III clinical trials. In this work, we analysed the in vitro effects of tofacitinib on the functions of human dendritic cells (DCs) and macrophages. When assessing the effects of tofacitinib on monocyte‐derived DCs, we observed reduced differentiation of monocytes into immature DCs, as evidenced by a decreased transcription of CD209 and CD80. Phenotype assessment in the presence of tofacitinib suggested a switch towards a M1‐like macrophage phenotype, as evidenced by the expression of M1 markers such as iNOS, as well as cytokines typically expressed by M1 cells, including IL‐12 and IL‐23. Of note, Arginase1 and CD200R, typically expressed by M2 cells, were absent on tofacitinib‐treated DCs. Furthermore, tofacitinib affected the response of differentiated DCs to maturation stimuli such as LPS and IFNγ, resulting in a partial up‐regulation of IL‐23 and down‐regulation of IL‐12, as assessed by qPCR. When investigating macrophage development, we found that tofacitinib inhibited the ability of monocytes to differentiate and polarize into regulatory M2 macrophages, while rather enhancing the ability to develop into inflammatory M1‐like macrophages, as evidenced by decreased expression of the M2 marker CD200R and enhanced production of IL‐12 and IL‐23. In conclusion, tofacitinib impacts the differentiation of human DCs and macrophages, it particularly favours generation of M1‐like pro‐inflammatory macrophages.

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Keratinocyte-Derived IL-17E Contributes to Inflammation in Psoriasis

Cited by 78 publications

References 55 publications

IL-17A in Psoriasis and Beyond: Cardiovascular and Metabolic Implications

IL-17A in Psoriasis and Beyond: Cardiovascular and Metabolic Implications

IL-25 enhances TH17 cell–mediated contact dermatitis by promoting IL-1β production by dermal dendritic cells

The Janus Kinase inhibitor tofacitinib impacts human dendritic cell differentiation and favours M1 macrophage development

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