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白细胞介素-17 在银屑病和银屑病关节炎中的作用。

Role of IL-17 in psoriasis and psoriatic arthritis.

机构信息

VA Sacramento Medical Centre, 10535, Hospital Way, Mather, CA 95655, USA.

出版信息

Clin Rev Allergy Immunol. 2013 Apr;44(2):183-93. doi: 10.1007/s12016-012-8307-1.

Abstract

The role of T cell subpopulations in human disease is in a transition phase due to continuous discovery of new subsets of T cell, one of which is Th17, characterized by the production of signature cytokine IL-17. In the last couple of years, many articles are coming out on the role of Th17 and its signature cytokine IL-17 in different autoimmune diseases like rheumatoid arthritis, psoriasis, psoriatic arthritis (PsA), SLE and multiple sclerosis. Psoriasis and PsA are immune-mediated diseases, affecting the skin and joints, respectively. Initially, it was thought that psoriasis and PsA were Th1-mediated diseases; however, studies in knockout animal models (IL-17 knockout mice) as well as human experimental data indicate that Th17 and its signature cytokine IL-17 have a critical role in the pathogenesis of psoriatic disease. Th17 cells have been identified from the dermal extracts of psoriatic lesions. Subsequently, our research group has substantiated this observation that Th17 cells are enriched in the papillary dermis of psoriatic plaques and in freshly isolated effector T lymphocytes from the synovial fluid of PsA patients, and we have reported that the majority of these CD4 + IL-17+ T cells are of memory phenotype (CD4RO(+)CD45RA(-)CD11a(+)). Recent reports also suggest that the synovial tissue in psoriatic arthritis is enriched with IL-17R, and its most well recognized receptor IL-17RA is functionally active in psoriatic arthritis. In this review article, we have discussed the role of IL-17 in psoriatic disease and have narrated about the novel IL17/IL-17R antibodies currently in preparation for its therapeutic uses in autoimmune diseases.

摘要

Th17 细胞及其特征性细胞因子白细胞介素-17(IL-17)在不同的自身免疫性疾病(如类风湿关节炎、银屑病、银屑病关节炎、系统性红斑狼疮和多发性硬化症)中的作用,正不断有新的研究结果发表,这表明 T 细胞亚群在人类疾病中的作用正处于转变阶段。在过去的几年中,许多关于 Th17 及其特征性细胞因子 IL-17 在不同自身免疫性疾病中的作用的文章相继发表。银屑病和银屑病关节炎是免疫介导的疾病,分别影响皮肤和关节。最初,人们认为银屑病和银屑病关节炎是 Th1 介导的疾病;然而,在基因敲除动物模型(IL-17 基因敲除小鼠)以及人类实验数据的研究表明,Th17 及其特征性细胞因子 IL-17 在银屑病发病机制中具有关键作用。已经从银屑病皮损的真皮提取物中鉴定出 Th17 细胞。随后,我们的研究小组证实了这一观察结果,即 Th17 细胞在银屑病斑块的乳头真皮中以及从银屑病关节炎患者的滑液中分离的新鲜效应 T 淋巴细胞中富集,并且我们已经报道了这些 CD4+IL-17+T 细胞中的大多数是记忆表型(CD4RO(+)CD45RA(-)CD11a(+))。最近的报告还表明,银屑病关节炎的滑膜组织富含白细胞介素-17 受体(IL-17R),其最被认可的受体白细胞介素-17A(IL-17RA)在银屑病关节炎中具有功能活性。在这篇综述文章中,我们讨论了白细胞介素-17 在银屑病发病机制中的作用,并讲述了目前正在为自身免疫性疾病的治疗用途而准备的新型 IL17/IL-17R 抗体。

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