Function and Role of Regulatory T Cells in Rheumatoid Arthritis

Abstract

Rheumatoid arthritis (RA) is a systemic and heterogeneous autoimmune disease with symmetrical polyarthritis as its critical clinical manifestation. The basic cause of autoimmune diseases is the loss of tolerance to self or harmless antigens. The loss or functional deficiency of key immune cells, regulatory T (Treg) cells, has been confirmed in human autoimmune diseases. The pathogenesis of RA is complex, and the dysfunction of Tregs is one of the proposed mechanisms underlying the breakdown of self-tolerance leading to the progression of RA. Treg cells are a vital component of peripheral immune tolerance, and the transcription factor Foxp3 plays a major immunosuppressive role. Clinical treatment for RA mainly utilizes drugs to alleviate the progression of disease and relieve disease activity, and the ideal treatment strategy should be to re-induce self-tolerance before obvious tissue injury. Treg cells are one of the ideal options. This review will introduce the classification, mechanism of action, and characteristics of Treg cells in RA, which provides insights into clinical RA treatment.

Keywords: Treg cells; autoimmune diseases; immune tolerance; rheumatoid arthritis; transcription factor Foxp3.

Figure 1

Mechanisms of Treg suppression. CTLA-4 binds to CD80/CD86 on DCs, inhibits the maturation and antigen presentation function of DCs and increases the expression of IDO in DCs, resulting in T effector incompetence. PD-1 binds to PD-L ligands on DCs and T cells to inhibit effector T cells, and synergistically enhance the transactivation of Smad3 by TGF-β.TIGIT increases IL-10 expression and decreases IL-12 expression in DCs by binding to CD155 on DCs and inhibits the activation of effector T cells. Tregs selectively inhibit the proinflammatory immune response mediated by Th1 and Th17 cells. The Th2-related transcription factor IRF-4 activates Treg expression through ICOS and CTLA-4, which restricts the Th2-mediated immune response. STAT3 increases the expression of the IL-10, Ebi3, and perforin-1 genes.