Regulatory T cells shield muscle mitochondria from interferon-γ-mediated damage to promote the beneficial effects of exercise

Exercise enhances physical performance and reduces the risk of many disorders such as cardiovascular disease, type 2 diabetes, dementia, and cancer. Exercise characteristically incites an inflammatory response, notably in skeletal muscles. Although some effector mechanisms have been identified, regu...

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Bibliographic Details
Published in:	Science immunology Vol. 8; no. 89; p. eadi5377
Main Authors:	Langston, P Kent, Sun, Yizhi, Ryback, Birgitta A, Mueller, Amber L, Spiegelman, Bruce M, Benoist, Christophe, Mathis, Diane
Format:	Journal Article
Language:	English
Published:	United States 03-11-2023
Subjects:	Animals Diabetes Mellitus, Type 2 - metabolism Interferon-gamma Mice Mitochondria, Muscle T-Lymphocytes, Regulatory Transcription Factors - metabolism
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Summary:	Exercise enhances physical performance and reduces the risk of many disorders such as cardiovascular disease, type 2 diabetes, dementia, and cancer. Exercise characteristically incites an inflammatory response, notably in skeletal muscles. Although some effector mechanisms have been identified, regulatory elements activated in response to exercise remain obscure. Here, we have addressed the roles of Foxp3 CD4 regulatory T cells (T ) in the healthful activities of exercise via immunologic, transcriptomic, histologic, metabolic, and biochemical analyses of acute and chronic exercise models in mice. Exercise rapidly induced expansion of the muscle T compartment, thereby guarding against overexuberant production of interferon-γ and consequent metabolic disruptions, particularly mitochondrial aberrancies. The performance-enhancing effects of exercise training were dampened in the absence of T . Thus, exercise is a natural T booster with therapeutic potential in disease and aging contexts.
ISSN:	2470-9468
DOI:	10.1126/sciimmunol.adi5377