Department of Dermatology, University of Cologne, Cologne, Germany.
Division of Dermatology and Venereology, Geneva University Hospitals, Geneva, Switzerland.
Front Immunol. 2020 Jan 15;10:3096. doi: 10.3389/fimmu.2019.03096. eCollection 2019.
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.
白细胞介素 17A（IL-17A）是目前已知的白细胞介素 17 细胞因子家族的六个成员之一，与针对感染病原体的免疫反应以及银屑病等炎症性自身免疫性疾病的发病机制有关。银屑病皮肤的特点是高水平表达 IL-17A 和 IL-17F，它们作用于免疫和非免疫细胞类型，强烈促进组织炎症。在银屑病病变中，IL-17A、IL-17E 和 IL-17F 参与中性粒细胞的积累，随后形成表皮微脓肿。IL-17A 与其他 Th17 细胞因子一起还上调了几种趋化因子的产生，这些趋化因子与银屑病发病机制有关。针对 IL-17A 的抗体在银屑病患者中显示出令人印象深刻的临床疗效。研究报告称，用抗-IL-17A 治疗的患者中，至少有 80%的患者经银屑病面积和严重程度指数（PASI）测量得到了至少 75%的改善。银屑病皮肤表现、心血管疾病以及银屑病代谢疾病似乎具有围绕 IL-17A 及其促炎作用演变的共同发病机制。因此，抗-IL-17A 治疗不仅改善了银屑病的皮肤表现，还改善了心血管炎症以及代谢因素和不同领域的银屑病关节炎（PsA），包括外周关节炎、附着点炎、指（趾）炎和轴向受累。本综述总结了 IL-17A 的生物学作用，然后回顾了其在皮肤生理和病理生理学以及心血管和代谢系统中的作用的现有数据。总之，根据目前可用的数据，为中重度银屑病患者提供了临床建议。
