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

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.