Weinstein Jessica E, Pepple Kathryn L
University of Washington, Department of Ophthalmology, Seattle, Washington, USA.
Curr Opin Ophthalmol. 2018 May;29(3):267-274. doi: 10.1097/ICU.0000000000000466.
Increasing evidence supports Th17 cells as key mediators of ocular inflammatory disease. Cytokines that are important for the development and pathologic function of these cells are potential therapeutic targets in patients with immune mediated uveitis. This review provides an overview of these cytokines including recent insights about their roles in ocular inflammation from laboratory and clinical studies.
Interleukin (IL)-6, IL-10, IL-17, IL-22, IL-23 and tumour necrosis factor-alpha (TNFα) are cytokines that have been examined for their functional role in uveitis and their relationship to pathologic Th17 cells. Studies in animal models, particularly in experimental autoimmune uveitis (EAU), have been instrumental in studying the role of these cytokines in disease pathogenesis. More recently, studies on aqueous, vitreous and serum from patients with uveitis using flow cytometry and multiplex ELISA bead-based methodologies have provided insights into the contribution of Th17 cells and the related cytokines in ocular inflammatory diseases. The central role of IL-23 in determining the pathologic Th17 fate has made it an effective therapeutic target in systemic diseases such as psoriasis and thereby an attractive potential target for patients with immune-mediated uveitis.
Th17 cells, and their related cytokines, are important inflammatory mediators in autoimmune uveitis. Animal and human studies continue to provide new information to direct development of new cytokine-targeted therapies for patients with uveitis.
越来越多的证据支持Th17细胞是眼部炎性疾病的关键介质。对这些细胞的发育和病理功能至关重要的细胞因子是免疫介导性葡萄膜炎患者潜在的治疗靶点。本综述概述了这些细胞因子,包括来自实验室和临床研究的关于它们在眼部炎症中作用的最新见解。
白细胞介素(IL)-6、IL-10、IL-17、IL-22、IL-23和肿瘤坏死因子-α(TNFα)是已被研究其在葡萄膜炎中的功能作用及其与病理性Th17细胞关系的细胞因子。动物模型研究,尤其是实验性自身免疫性葡萄膜炎(EAU)研究,在研究这些细胞因子在疾病发病机制中的作用方面发挥了重要作用。最近,使用流式细胞术和基于多重ELISA微珠的方法对葡萄膜炎患者的房水、玻璃体和血清进行的研究,为Th17细胞和相关细胞因子在眼部炎性疾病中的作用提供了见解。IL-23在决定病理性Th17命运方面的核心作用使其成为银屑病等全身性疾病的有效治疗靶点,从而成为免疫介导性葡萄膜炎患者有吸引力的潜在靶点。
Th17细胞及其相关细胞因子是自身免疫性葡萄膜炎中重要的炎症介质。动物和人体研究继续提供新信息,以指导针对葡萄膜炎患者开发新的细胞因子靶向疗法。