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Prog Mol Biol Transl Sci. 2015;136:207-15. doi: 10.1016/bs.pmbts.2015.07.021. Epub 2015 Aug 28.

Regulatory T cells in Arthritis.

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Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan; Japan Science and Technology Agency, Exploratory Research for Advanced Technology Program, Takayanagi Osteonetwork Project, Bunkyo-ku, Tokyo, Japan. Electronic address:


Rheumatoid arthritis (RA) is one of the most common autoimmune diseases and is characterized by inflammation and subsequent bone destruction in multiple joints. In mice, depletion of regulatory T (Treg) cells results in the onset of a variety of autoimmune diseases including arthritis, while replenishment of Treg cells alleviates arthritic symptoms. The importance of Treg cells in RA is supported by the effectiveness of CTLA4-Ig therapy, an increased Treg cell/effector T cell ratio after anti-IL-6R or anti-TNF-α treatment and the identification of CTLA-4 as an RA-associated gene. Thus, Treg cells constitute a useful target in the treatment of RA. Foxp3(+) T cells consist of heterogeneous populations in terms of their surface markers, suppressive function, and plasticity. Plastic Foxp3(+) T cells are able to convert into pathogenic Th17 cells, which have been shown to exacerbate arthritis in mice. Therefore, it is important to identify a stable suppressive Foxp3(+) Treg cell subpopulation along with suppressive molecules and surface markers. In addition, considering the recent studies on the identification of arthritic antigens, the generation of antigen-specific Treg cells from naïve CD4(+) T cells or effector T cells is now feasible, along with the induction of Foxp3 and stabilization of the suppressive function by epigenetic modification of Treg cell signature genes. These approaches will lead to the establishment of new therapeutic strategies against arthritis that work by increasing the Treg cell/effector T cell ratio in favor of Treg cells. Here, we summarize our understanding of the role of Treg cells in arthritis based on recent human and murine studies.


Antigen-specificity; CTLA-4; Epigenetic modification; IL-6; Osteoclast; Plasticity; Rheumatoid arthritis; TNF-α

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