Characteristics of PD‐1+CD4+ T cells in peripheral blood and synovium of rheumatoid arthritis patients

Abstract

Abstract Objectives PD‐1 plays a crucial role in the immune dysregulation of rheumatoid arthritis (RA), but the specific characteristics of PD‐1+CD4+ T cells remain unclear and require further investigation. Methods Circulating PD‐1+CD4+ T cells from RA patients were analysed using flow cytometry. Plasma levels of soluble PD‐1 (sPD‐1) were measured using enzyme‐linked immunosorbent assay (ELISA). Single‐cell RNA sequence data from peripheral blood mononuclear cells (PBMCs) and synovial tissue of patients were obtained from the GEO and the ImmPort databases. Bioinformatics analyses were performed in the R studio to characterise PD‐1+CD4+ T cells. Expression of CCR7, KLF2 and IL32 in PD‐1+CD4+ T cells was validated by flow cytometry. Results RA patients showed an elevated proportion of PD‐1+CD4+ T cells in peripheral blood, along with increased plasma sPD‐1 levels, which positively correlated with TNF‐α and erythrocyte sedimentation rate. Bioinformatic analysis revealed PD‐1 expression on CCR7+CD4+ T cells in PBMCs, and on both CCR7+CD4+ T cells and CXCL13+CD4+ T cells in RA synovium. PD‐1 was co‐expressed with CCR7, KLF2, and IL32 in peripheral CD4+ T cells. In synovium, PD‐1+CCR7+CD4+ T cells had higher expression of TNF and LCP2, while PD‐1+CXCL13+CD4+ T cells showed elevated levels of ARID5A and DUSP2. PD‐1+CD4+ T cells in synovium also appeared to interact with B cells and fibroblasts through BTLA and TNFSF signalling pathways. Conclusion This study highlights the increased proportion of PD‐1+CD4+ T cells and elevated sPD‐1 levels in RA. The transcriptomic profiles and signalling networks of PD‐1+CD4+ T cells offer new insights into their role in RA pathogenesis.

Keywords

• CD4+ T cells
• PD‐1
• rheumatoid arthritis
• single‐cell RNA‐seq
• soluble PD‐1