IL-17 in inflammatory skin diseases psoriasis and hidradenitis suppurativa. (8th June 2020)

• Record Type: Journal Article
• Authors: Fletcher, J M; Moran, B; Petrasca, A; Smith, C M
• Is Part Of: Clinical and experimental immunology. Volume 201:Number 2(2020)
• Page Start: 121
• Page End: 134
• Publication Date: 2020-06-08
• Subjects: hidradenitis suppurativa -- IL-17 -- psoriasis; Immunopathology -- Periodicals; 616.079
• DOI: 10.1111/cei.13449
• Languages: English
• ISSNs: 0009-9104

Abstract

Summary: The skin is one of the most important organs in the body, providing integrity and acting as a barrier to exclude microbes, allergens and chemicals. However, chronic skin inflammation can result when barrier function is defective and immune responses are dysregulated or misdirected against harmless or self-antigens. During the last 15 years interleukin (IL)-17 cytokines have emerged as key players in multiple inflammatory disorders, and they appear to be especially prominent in skin inflammation. IL-17 cytokines produced by T cells and other cell types potently activate keratinocytes to promote inflammation in a feed-forward loop. Given this key pathogenic role of the IL-17 pathway in autoimmune and inflammatory disease, it has been the focus of intense efforts to target therapeutically. The inflammatory effects of IL-17 can be targeted directly by blocking the cytokine or its receptor, or indirectly by blocking cytokines upstream of IL-17-producing cells. Psoriasis has been the major success story for anti-IL-17 drugs, where they have proven more effective than in other indications. Hidradenitis suppurativa (HS) is another inflammatory skin disease which, despite carrying a higher burden than psoriasis, is poorly recognized and under-diagnosed, and current treatment options are inadequate. Recently, a key role for the IL-17 pathway in the pathogenesis of HS has emerged, prompting clinical trials with a variety of IL-17 inhibitors. In this review, we discuss the roles of IL-17A, IL-17F and IL-17C in psoriasis and HS and the strategies taken to target the IL-17 pathway therapeutically. Graphical Abstract: