Comprehensive TCR repertoire analysis of CD4+ T-cell subsets in rheumatoid arthritis.

Abstract

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-naïve RA patients and healthy controls were sorted into seven subsets including naïve, effector, central memory, effector memory (EMT), Th1, Th17, and regulatory T cells. T-cell receptor β 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.

• Authors: Xu Jiang, Shiyu Wang, Chen Zhou, Jinghua Wu, Yuhao Jiao, Liya Lin, Xin Lu, Bo Yang, Wei Zhang, Xinyue Xiao, Yueting Li, Xunyao Wu, Xie Wang, Hua Chen, Lidan Zhao, Yunyun Fei, Huaxia Yang, Wen Zhang, Fengchun Zhang, Hui Chen, Jianmin Zhang, Bin Li, Huanming Yang, Jian Wang, Xiao Liu, Xuan Zhang
• Journal: Journal of autoimmunity (J Autoimmun) Vol. 109 Pg. 102432 (05 2020) ISSN: 1095-9157 [Electronic] England
• PMID: 32115259 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Ltd. All rights reserved.

Chemical References

• Biomarkers
• Receptors, Antigen, T-Cell

Topics

• Arthritis, Rheumatoid (etiology, metabolism, pathology)
• Biomarkers
• CD4-Positive T-Lymphocytes (immunology, metabolism, pathology)
• Cells, Cultured
• Disease Susceptibility
• Humans
• Lymphocyte Activation
• Receptors, Antigen, T-Cell (metabolism)
• T-Lymphocyte Subsets (immunology, metabolism, pathology)