Journal
JOURNAL OF AUTOIMMUNITY
Volume 109, Issue -, Pages -Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jaut.2020.102432
Keywords
Rheumatoid arthritis; T-cell receptor repertoires; Th17; Effector memory T cell
Categories
Funding
- National Natural Science Foundation of China [81788101, 81630044, 81601432, 81550023, 81325019, 81771763, 81273312, 91542000, 81801633, 81701623]
- Chinese Academy of Medical Science Innovation Fund for Medical Sciences, China [CIFMS2016-12M-1-003, 2017-12M-1-008, 2017-I2M-3-011, 2016-12M-1-008]
- National Key Research and Development Program: Precise Medical Research, China [2016YFC0903900]
- Medical Epigenetics Research Center, Chinese Academy of Medical Sciences, China [2017PT31035]
- Shenzhen Municipal Government of China [JCYJ20170817145404433, JCYJ20170817145428361]
- Construction Project of National Traditional Chinese Medicine Clinical Research Base of SATCM
- Clinical Cooperative Project of Chinese and Western Medicine for Major and Knotty Diseases of SATCM, China
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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.
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