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银屑病关节炎先天免疫的最新遗传学进展。

Recent genetic advances in innate immunity of psoriatic arthritis.

机构信息

Department of Dermatology, University of Michigan, Ann Arbor 48109, MI, USA.

Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.

出版信息

Clin Immunol. 2020 May;214:108405. doi: 10.1016/j.clim.2020.108405. Epub 2020 Apr 2.

Abstract

Psoriatic arthritis (PsA) is a heterogeneous disease that affects multiple organ systems including the peripheral and axial joints, entheses and nails. PsA is associated with significant comorbidities including cardiovascular, metabolic, and psychiatric diseases. The pathogenesis of PsA is complex and involves genetic, immunologic and environmental factors. Recent evidence suggests the heritability for PsA to be stronger and distinct from that of PsC. Prominent genes identified via GWAS for PsA include HLA-B/C, HLAB, IL12B, IL23R, TNP1, TRAF3IP3, and REL. We review the genetics of psoriatic arthritis and discuss the role of the innate immune system as important in the pathogenesis of PsA by focusing on key signaling pathways and cellular makeup. Understanding the candidate genes identified in PsA highlights pathways of critical importance to the pathogenesis of psoriatic disease including the key role of the innate immune response, mediated through IL-23/IL-17 axis, RANK and NFκB signaling pathways.

摘要

银屑病关节炎(PsA)是一种异质性疾病,影响包括外周和轴向关节、附着点和指甲在内的多个器官系统。PsA 与多种合并症相关,包括心血管、代谢和精神疾病。PsA 的发病机制复杂,涉及遗传、免疫和环境因素。最近的证据表明,PsA 的遗传性更强,与 PsC 不同。通过全基因组关联研究(GWAS)确定的突出基因包括 HLA-B/C、HLAB、IL12B、IL23R、TNP1、TRAF3IP3 和 REL。我们回顾了银屑病关节炎的遗传学,并通过关注关键信号通路和细胞组成,讨论了固有免疫系统在 PsA 发病机制中的重要作用。了解在 PsA 中确定的候选基因突出了对银屑病发病机制至关重要的途径,包括通过 IL-23/IL-17 轴、RANK 和 NFκB 信号通路介导的固有免疫反应的关键作用。

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