Single cell sequencing identifies clonally expanded synovial CD4+ TPH cells expressing GPR56 in rheumatoid arthritis
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
Abstract
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.