FoxP3+ regulatory T cells in the peripheral blood and synovial fluid of patients with rheumatoid arthritis

Abstract

Human regulatory T (Treg) cells expressing the transcription factor forkhead box P3 (FoxP3) are indispensable for self-tolerance and immune homeostasis. Abnormal Treg cell counts and impaired function have been implicated in the development of various autoimmune diseases. The Treg cell counts in the peripheral blood of subjects with rheumatoid arthritis (RA) vary, probably due to heterogeneity of the Treg cells. Recent studies demonstrated that human FoxP3+ Treg cell populations actually include three functionally distinct subpopulations, and that CD45RA-FoxP3high effector Treg cells are significantly decreased in the peripheral blood of patients with RA. On the other hand, it is generally agreed that the frequency of FoxP3+ Treg cells in synovial fluid is higher in patients with RA than in healthy controls. Although these findings were initially considered paradoxical, a recent study revealed that in RA patients, most of the cells in the FoxP3+ Treg population of the synovial fluid are actually non-suppressive cytokine-producing CD45RA-FoxP3low non-Treg cells. The imbalance between FoxP3+ Treg cell subpopulations in the circulation and at inflammation sites may contribute to the pathogenesis of RA.