Frontiers in Immunology ( IF 7.3 ) Pub Date : Esther von Stebut, Wolf-Henning Boehncke, Kamran Ghoreschi, Tommaso Gori, Ziya Kaya, Diamant Thaci, Andreas Schäffler
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.
中文翻译:
IL-17A在牛皮癣及其他方面:心血管和代谢的影响
白介素17A(IL-17A)是IL-17细胞因子家族中目前已知的六个成员之一,与传染性病原体的免疫反应以及炎性自身免疫性疾病(如牛皮癣)的发病机制有关。银屑病皮肤的特征在于IL-17A和IL-17F的高表达,它们作用于免疫和非免疫细胞类型,并强烈促进组织炎症。在银屑病皮损中,IL-17A,IL-17E和IL-17F参与嗜中性粒细胞的积累,随后形成表皮微脓肿。IL-17A与其他Th17细胞因子一起也上调了与牛皮癣发病机理有关的几种趋化因子的产生。IL17A靶向抗体在牛皮癣患者中显示出令人印象深刻的临床疗效。研究报告称,以牛皮癣面积和严重程度指数(PASI)衡量,在接受抗IL-17A治疗的患者中,> 80%的患者至少改善了75%。牛皮癣的皮肤表现,心血管疾病以及牛皮癣的代谢性疾病似乎共享围绕IL-17A进化的致病机制及其促炎作用。因此,抗IL-17A疗法不仅改善牛皮癣的皮肤表现,而且改善心血管炎症以及新陈代谢因子和牛皮癣关节炎(PsA)的不同领域,包括外周关节炎,皮炎,齿根炎和轴向受累。这篇综述总结了IL-17A的生物学作用,然后回顾了其在皮肤的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。结论,