类风湿性关节炎
细胞毒性T细胞
免疫学
CXCL13型
T细胞
滑膜
生物
受体
滑液
关节炎
白细胞介素21
分子生物学
免疫系统
医学
病理
趋化因子
遗传学
趋化因子受体
体外
替代医学
骨关节炎
作者
Alexandra Argyriou,Marc H. Wadsworth,Adrian Lendvai,Stephen M. Christensen,Aase Hensvold,Christina Gerstner,Annika van Vollenhoven,Kellie M. Kravarik,Aaron Winkler,Vivianne Malmström,Karine Chemin
标识
DOI:10.1038/s41467-022-31519-6
摘要
Abstract Rheumatoid arthritis (RA) is an autoimmune disease affecting synovial joints where different CD4 + T cell subsets may contribute to pathology. Here, we perform single cell sequencing on synovial CD4 + T cells from anti-citrullinated protein antibodies (ACPA)+ and ACPA- RA patients and identify two peripheral helper T cell (T PH ) states and a cytotoxic CD4 + T cell subset. We show that the adhesion G-protein coupled receptor 56 (GPR56) delineates synovial CXCL13 high T PH CD4 + T cells expressing LAG-3 and the tissue-resident memory receptors CXCR6 and CD69. In ACPA- SF, T PH cells display lower levels of GPR56 and LAG-3. Further, most expanded T cell clones in the joint are within CXCL13 high T PH CD4 + T cells. Finally, RNA-velocity analyses suggest a common differentiation pathway between the two T PH clusters and effector CD4 + T cells. Our study provides comprehensive immunoprofiling of the synovial CD4 + T cell subsets in ACPA+ and ACPA- RA.
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