Key Points
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Regulatory T (TREG) cells maintain immunological tolerance and prevent autoimmunity by inhibiting the activation and proliferation of immune effector cells
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Constitutive expression and induced expression of forkhead box protein 3 (FOXP3) are hallmarks of natural TREG cells and peripheral TREG cells, respectively
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Human FOXP3-expressing cells are heterogeneous and some FOXP3+CD4+ T cells are not immunosuppresive
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Defective TREG-cell function in mice can cause multisystemic diseases, including rheumatic diseases
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Abnormal TREG-cell number and function are common in patients with rheumatic diseases, including systemic lupus erythematosus and rheumatoid arthritis
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Based on the current knowledge of TREG-cell biology, several therapeutic strategies could be used to treat rheumatic diseases: in vitro expansion, in vivo expansion or in vitro induction of antigen-specific TREG cells
Abstract
Naturally occurring Foxp3+CD25+CD4+ regulatory T (TREG) cells maintain immunological self-tolerance and prevent a variety of autoimmune diseases, including rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus. In animal models of rheumatic disease, autoimmune responses can be controlled by re-establishing the T-cell balance in favour of TREG cells. Here we discuss three potential strategies for the clinical use of TREG cells to treat autoimmune rheumatic disease: expansion of self-antigen-specific natural TREG cells in vivo; propagation of antigen-specific natural TREG cells ex vivo, by in vitro antigenic stimulation, and subsequent transfer back into the host; or conversion of antigen-specific conventional T cells into TREG cells in vivo or ex vivo. These strategies require depletion of the effector T cells that mediate autoimmunity before initiating TREG-cell-based therapies. Immunotherapies that target TREG cells, and the balance of TREG cells and autoreactive T cells, are therefore an important modality for the treatment of autoimmune rheumatic disease.
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Acknowledgements
M.M. was supported by Association Lupus France, SNFMI, Association Francophone contre la Polychondrite Chronique Atrophiante and by Fondation ARTHRITIS Courtin. S.S. was supported by Grants-in-Aid for Specially Promoted Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan and by Core Research for Evolutional Science and Technology (CREST) from Japan Science and Technology Agency.
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Miyara, M., Ito, Y. & Sakaguchi, S. TREG-cell therapies for autoimmune rheumatic diseases. Nat Rev Rheumatol 10, 543–551 (2014). https://doi.org/10.1038/nrrheum.2014.105
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DOI: https://doi.org/10.1038/nrrheum.2014.105
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Bee venom phospholipase A2 alleviates collagen-induced polyarthritis by inducing Foxp3+ regulatory T cell polarization in mice
Scientific Reports (2021)