Work

Engaging PD-1 rescuesregulatory T cell function and inhibits inflammatory T cells in rheumatoid arthritis

Year: 2025

Type: article

Abstract: BACKGROUND: Despite their synovial enrichment, regulatory T cells (Treg) fail to alleviate the joint inflammation in rheumatoid arthritis (RA). This indicates their functional impairment in the synovial milieu of RA patients. RESULTS: Here, we demonstrate that a deficit in the PD-1 pathway incapacitates the synovial Treg cells, and engaging programmed cell death protein-1 (PD-1) restores their suppressive function (interleukin 10, transforming growth factor beta secretion), which in turn suppresses the synovial inflammatory T cells (IFN-γ+, IL-17+ TNF-α+). We also showed that a deficit in programmed death ligand-1 expression on RA synovial macrophages contributes to impaired Treg cell function. CONCLUSION: Rejuvenating synovial Treg cell function via PD-1 engagement may be a potential strategy to ameliorate the synovial inflammation in RA patients.

Source: Clinical & Experimental Immunology

DOI: 10.1093/cei/uxaf035