IL-17E (IL-25) Enhances Innate Immune Responses during Skin Inflammation

Senra, Luisa; Mylonas, Alessio; Kavanagh, Ruairi D.; Fallon, Padraic G.; Conrad, Curdin; Borowczyk, Julia; Wrobel, Ludovic J.; Kaya, Gürkan; Yawalkar, Nikhil; Boehncke, Wolf‐Henning; Brembilla, Nicolò Costantino

doi:10.1016/j.jid.2019.01.021

Cited by 47 publications

(47 citation statements)

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“…In atopic dermatitis, IL-17E was shown to impair the proper epidermal barrier formation (Deleuran et al, 2012;Hvid et al, 2011). In psoriasis, we identified that keratinocytes overproduce IL-17E, leading to inflammatory events favoring the recruitment of neutrophils (Senra et al, 2019(Senra et al, , 2016. Later studies confirmed our observations and reported an autocrine function for IL-17E in mouse keratinocytes (Xu et al, 2018).…”

Section: Introductionsupporting

confidence: 75%

“…IL-17A is likely the most important factor driving psoriasis, as demonstrated by the high efficacy of antieIL-17A targeted therapies (Yiu and Griffiths, 2016). Previously, we demonstrated that IL-17E amplifies the inflammatory loop in psoriasis by acting on immune cells (Senra et al, 2019(Senra et al, , 2016. Here we document the capacity of IL-17E to target keratinocytes in an autocrine manner.…”

Section: Discussionsupporting

confidence: 54%

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IL-17E (IL-25) and IL-17A Differentially Affect the Functions of Human Keratinocytes

Borowczyk

Buerger

Tadjrischi

et al. 2020

Journal of Investigative Dermatology

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Our group has recently shown that keratinocyte-derived IL-17E (IL-25), one of six members of the IL-17 family, is overexpressed in lesional psoriatic skin and is involved in its pathophysiology. We show here that IL-22 enhances IL-17E production in human keratinocytes and that these cells display a complete IL-17E receptor at their surface, the expression of which is further induced by IL-17A, indicating a potential autocrine effect of IL-17E. Therefore, we addressed the impact of IL-17E on the function of human primary keratinocytes. IL-17E promoted the proliferation of keratinocytes in two-dimensional and three-dimensional cultures and caused the concomitant upregulation of differentiation-associated gene transcripts (e.g., keratin 10), whereas their expression was either inhibited or not changed by IL-17A. Contrary to IL-17A, IL-17E was not involved in the induction of antimicrobial proteins. Time-lapse analysis of cell movement showed that IL-17E influences cell motility, increasing both cell speed and displacement. This was associated with specific changes in the actin cytoskeleton organization and the cell-substrate adhesion. No such effects were observed upon IL-17A stimulation. In summary, we identified effects of IL-17E clearly distinct from IL-17A, pointing toward an important role of IL-17E in the physiology and pathophysiology of the epidermis.

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Section: Introductionsupporting

confidence: 75%

Section: Discussionsupporting

confidence: 54%

IL-17E (IL-25) and IL-17A Differentially Affect the Functions of Human Keratinocytes

Borowczyk

Buerger

Tadjrischi

et al. 2020

Journal of Investigative Dermatology

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“…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%

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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“…The T helper 17 (Th17) cells constitute a unique subset of CD4 + T cells and are the major source of IL-17 (5). IL-17A triggers cellular reactions not only in the keratinocytes, but also in some other cells, including neutrophils, endothelial cells, fibroblasts, and osteoclasts (6)(7)(8)(9)(10). In keratinocytes, the binding of IL-17A to IL-17 receptor (IL-17R) A, IL-17C, or IL-17RD stimulates keratinocyte proliferation.…”

Section: Introductionmentioning

confidence: 99%

The IL-23/IL-17 Pathway in Inflammatory Skin Diseases: From Bench to Bedside

et al. 2020

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Interleukin-17 (IL-17) is an essential proinflammatory cytokine, which is mainly secreted by the CD4 + helper T cells (Th17 cells) and subsets of innate lymphoid cells. IL-17A is associated with the pathogenesis of inflammatory diseases, including psoriasis, atopic dermatitis, hidradenitis suppurativa, alopecia areata, pityriasis rubra pilaris, pemphigus, and systemic sclerosis. Interleukin-23 (IL-23) plays a pivotal role in stimulating the production of IL-17 by activating the Th17 cells. The IL-23/IL-17 axis is an important pathway for targeted therapy for inflammatory diseases. Emerging evidence from clinical trials has shown that monoclonal antibodies against IL-23, IL-17, and tumor necrosis factor are effective in the treatment of patients with psoriasis, atopic dermatitis, hidradenitis suppurativa, pityriasis rubra pilaris, pemphigus, and systemic sclerosis. Here, we summarize the latest knowledge about the biology, signaling, and pathophysiological functions of the IL-23/IL-17 axis in inflammatory skin diseases. The currently available biologics targeting the axis is also discussed.

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IL-17E (IL-25) Enhances Innate Immune Responses during Skin Inflammation

Cited by 47 publications

References 50 publications

IL-17E (IL-25) and IL-17A Differentially Affect the Functions of Human Keratinocytes

IL-17E (IL-25) and IL-17A Differentially Affect the Functions of Human Keratinocytes

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

The IL-23/IL-17 Pathway in Inflammatory Skin Diseases: From Bench to Bedside

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