Comprehensive TCR repertoire analysis of CD4+ T-cell subsets in rheumatoid arthritis
Comprehensive TCR repertoire analysis of CD4+ T-cell subsets in rheumatoid arthritis
复制标题
类风湿性关节炎中 CD4(+) T 细胞亚群的综合 TCR 谱分析。
DOI：
10.1016/j.jaut.2020.102432
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发表时间：
2020-05-01
影响因子：
12.8
通讯作者：
Zhang, Xuan
中科院分区：
文献类型：
--
作者：
Jiang, Xu;Wang, Shiyu;Zhang, Xuan
类风湿性关节炎 (RA) 是一种全身性自身免疫性疾病，其特征是自身反应性 T 细胞积聚和促炎细胞因子过度产生，其发病机制尚不清楚。系统地研究不同 CD4(+) T 细胞亚群的 T 细胞受体 (TCR) 库有助于了解 RA 发病机制。在这里，来自初治 RA 患者和健康对照的外周 CD4(+) T 细胞被分为七个亚群，包括初始 T 细胞、效应细胞、中枢记忆细胞、效应记忆 (EMT)、Th1、Th17 和调节性 T 细胞。然后通过下一代测序分析 T 细胞受体 β 链库。我们在 RA 患者的 EMT 和 Th17 细胞中发现了 T 细胞克隆扩增，具有高度相似的 TCR 库。离体实验证明 RA 中 EMT 细胞优先分化为 Th17 细胞。值得注意的是，我们发现 TCR 多样性和 Th17 分化 T 细胞的丰度与 RA 疾病活动度显着相关。基于这些观察，我们提出从 EMT 到 Th17 的异常分化以及 Th17 的扩增在 RA 发病机制中发挥着关键作用。
The pathogenesis of rheumatoid arthritis (RA), a systemic autoimmune disease characterized by autoreactive T-cell accumulation and pro-inflammatory cytokine overproduction, is unclear. Systematically addressing T-cell receptor (TCR) repertoires of different CD4(+) T-cell subsets could help understand RA pathogenesis. Here, peripheral CD4(+) T cells from treatment-naive RA patients and healthy controls were sorted into seven subsets including naive, effector, central memory, effector memory (EMT), Th1, Th17, and regulatory T cells. T-cell receptor beta chain repertoires were then analyzed by next-generation sequencing. We identified T-cell clonal expansion in EMT and Th17 cells of RA patients, with highly similar TCR repertoires. Ex vivo experiments demonstrated the preferred differentiation from EMT to Th17 cells in RA. Notably, we showed that TCR diversity and abundance of differentiated T cells of Th17 were significantly correlated with RA disease activity. Based on these observations, we propose that abnormal differentiation from EMT to Th17 and expansion of Th17 play pivotal role in RA pathogenesis.