IL-17 and IL-17R: an auspicious therapeutic target for psoriatic disease
IL-17 and IL-17R: an auspicious therapeutic target for psoriatic disease
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DOI：
10.1016/s0001-7310(14)70015-8
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发表时间：
2014-10-01
影响因子：
3.2
通讯作者：
Raychaudhuri, S. P.
中科院分区：
文献类型：
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作者：
Mitra, A.;Raychaudhuri, S. K.;Raychaudhuri, S. P.
人类自身免疫性疾病中新的T细胞亚群的不断发现使免疫病理网络变得更加复杂。Th 17细胞是一种新鉴定的T细胞亚群，其特征在于产生标志性细胞因子IL-17。在过去的几年中，一些研究已经有力地确立了Th 17细胞及其标志性细胞因子IL-17在自身免疫性疾病中的调节作用，所述自身免疫性疾病包括银屑病、银屑病关节炎、类风湿性关节炎、炎性肠病、系统性红斑狼疮和多发性硬化症。银屑病和PsA是免疫介导的过度增殖性疾病，分别影响皮肤和关节。在Th 17细胞发现之前，银屑病和银屑病疾病被认为主要是Th 1介导的疾病;后来的IL-17敲除动物研究以及人体实验数据表明Th 17细胞及其标志性细胞因子IL- 17在这些疾病的发病机制中发挥着至关重要的作用。体外人体研究显示银屑病斑块中Th 17细胞的丰度。随后，我们的研究小组将这一观察扩展到银屑病关节炎中，发现滑液中大量的CD 4 + IL-17+ T细胞，并且这些T细胞中的大多数具有记忆表型（CD 4 RO + CD 45 RA-CD 11 a+）。此外，我们发现银屑病关节炎患者滑膜成纤维细胞中存在功能性IL-17受体。考虑到IL-17与银屑病疾病的强关联，IL-17靶向治疗在临床前和临床试验中显示出前景。本文综述了IL-17在银屑病发病中的作用，并总结了不同的抗IL-17治疗银屑病的疗效和安全性。(C)2014 Elsevier Espana，S.L. AEDV。版权所有
The continuous discovery of new T cell subpopulations in human autoimmune diseases is making the immunopathological network more complex. Th17 cells are one such newly identified subset of T cells, characterized by the production of signature cytokine IL-17. In last few years, several studies have strongly established the regulatory role of Th17 cells and its signature cytokine IL-17 in autoimmune diseases including psoriasis, psoriatic arthritis, rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus and multiple sclerosis. Psoriasis and PsA are immune mediated hyperproliferative diseases, affecting skin and joint respectively. Before the discovery of Th17 cells, psoriasis and psoriatic diseases were thought to be chiefly Th1 mediated diseases; later on IL-17 knockout animal studies as well as human experimental data indicate the crucial role of Th17 cells and its signature cytokine IL- 17 in the pathogenesis of these diseases. In vitro human studies have shown the abundance of Th17 cells in the psoriatic plaques. Subsequently our research group has extended this observation in psoriatic arthritis and found the abundance of CD4+ IL-17+ T cells in the synovial fluid and majority of these T cells are of memory phenotype (CD4RO+CD45RA- CD11a+). In addition, we showed the significant presence of functional IL-17 receptor in synovial fibroblast of psoriatic arthritis patients. Considering the strong association of IL-17 and psoriatic disease, IL-17 targeted therapy have shown promises in preclinical and clinical trials. In this review article, we have discussed the pathogenic role of IL-17 in psoriatic disease and summarized the therapeutic efficacy and safety profile of different anti IL-17 therapy as an anti-psoriatic agent. (C) 2014 Elsevier Espana, S.L. and AEDV. All rights reserved