IL‐17 in inflammatory skin diseases psoriasis and hidradenitis suppurativa

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.