Division of Rheumatology, Center for Molecular Medicine, Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Inflammation & Immunology Research Unit, Pfizer Inc., Cambridge, MA, 02139, USA.
Nat Commun. 2022 Jul 13;13(1):4046. doi: 10.1038/s41467-022-31519-6.
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) states and a cytotoxic CD4 T cell subset. We show that the adhesion G-protein coupled receptor 56 (GPR56) delineates synovial CXCL13 T CD4 T cells expressing LAG-3 and the tissue-resident memory receptors CXCR6 and CD69. In ACPA- SF, T cells display lower levels of GPR56 and LAG-3. Further, most expanded T cell clones in the joint are within CXCL13 T CD4 T cells. Finally, RNA-velocity analyses suggest a common differentiation pathway between the two T clusters and effector CD4 T cells. Our study provides comprehensive immunoprofiling of the synovial CD4 T cell subsets in ACPA+ and ACPA- RA.
类风湿关节炎（RA）是一种影响滑膜关节的自身免疫性疾病，其中不同的 CD4 T 细胞亚群可能导致发病机制。在这里，我们对抗瓜氨酸化蛋白抗体（ACPA）+和 ACPA-RA 患者的滑膜 CD4 T 细胞进行了单细胞测序，鉴定出两种外周辅助性 T 细胞（T）状态和一个细胞毒性 CD4 T 细胞亚群。我们发现，黏附 G 蛋白偶联受体 56（GPR56）可区分滑膜 CXCL13 T CD4 T 细胞，这些细胞表达 LAG-3 以及组织驻留记忆受体 CXCR6 和 CD69。在 ACPA-SF 中，T 细胞显示出较低水平的 GPR56 和 LAG-3。此外，关节中大多数扩增的 T 细胞克隆都存在于 CXCL13 T CD4 T 细胞中。最后，RNA 速度分析表明，两个 T 群和效应性 CD4 T 细胞之间存在共同的分化途径。我们的研究为 ACPA+和 ACPA-RA 患者的滑膜 CD4 T 细胞亚群提供了全面的免疫分析。
