Mitra A, Raychaudhuri S K, Raychaudhuri S P
VA Medical Center Sacramento, Mather, CA, USA; University of California, Davis, Dermatology, School of Medicine, Sacramento, CA, USA.
VA Medical Center Sacramento, Mather, CA, USA; University of California, Davis, School of Medicine, Internal Medicine/Rheumatology, Allergy & Clinical Immunology, Davis, CA, USA.
Actas Dermosifiliogr. 2014 Oct;105 Suppl 1:21-33. doi: 10.1016/S0001-7310(14)70015-8.
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.
人类自身免疫性疾病中新的T细胞亚群不断被发现，这使得免疫病理网络变得更加复杂。Th17细胞就是新发现的一类T细胞亚群，其特征是产生标志性细胞因子白细胞介素-17（IL-17）。在过去几年中，多项研究有力地证实了Th17细胞及其标志性细胞因子IL-17在包括银屑病、银屑病关节炎、类风湿关节炎、炎症性肠病、系统性红斑狼疮和多发性硬化症等自身免疫性疾病中的调节作用。银屑病和银屑病关节炎是免疫介导的过度增殖性疾病，分别影响皮肤和关节。在Th17细胞被发现之前，银屑病和银屑病相关疾病被认为主要是Th1介导的疾病；后来的IL-17基因敲除动物研究以及人体实验数据表明，Th17细胞及其标志性细胞因子IL-17在这些疾病的发病机制中起关键作用。体外人体研究显示银屑病斑块中存在大量Th17细胞。随后，我们的研究小组将这一观察结果扩展到银屑病关节炎，发现滑液中存在大量CD4+IL-17+T细胞，且这些T细胞大多具有记忆表型（CD4RO+CD45RA-CD11a+）。此外，我们还发现银屑病关节炎患者的滑膜成纤维细胞中存在功能性IL-17受体。鉴于IL-17与银屑病疾病的密切关联，IL-17靶向治疗在临床前和临床试验中已显示出前景。在这篇综述文章中，我们讨论了IL-17在银屑病疾病中的致病作用，并总结了不同抗IL-17治疗作为抗银屑病药物的治疗效果和安全性。
