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- Title
Regulatory T cells shield muscle mitochondria from interferon-γ–mediated damage to promote the beneficial effects of exercise.
- Authors
Langston, P. Kent; Sun, Yizhi; Ryback, Birgitta A.; Mueller, Amber L.; Spiegelman, Bruce M.; Benoist, Christophe; Mathis, Diane
- Abstract
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 (Tregs) 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 Treg 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 Tregs. Thus, exercise is a natural Treg booster with therapeutic potential in disease and aging contexts. Editor's summary: Regulatory T cells (Tregs) support repair of injured muscle, but whether they participate in the response of healthy muscle to exercise training remains unclear. Using acute and chronic models of exercise in mice, Langston et al. found that Tregs suppress exercise-induced skeletal muscle inflammation that is counterproductive for performance enhancement. Tregs were required for gains in exercise capacity and promoted muscle metabolic reprogramming by protecting mitochondria from interferon-γ–driven damage. These results identify Tregs as a key regulatory element that is activated in response to exercise and needed to support performance-enhancing muscle adaptations. —Claire Olingy
- Subjects
REGULATORY T cells; MUSCLE cells; AEROBIC capacity; MITOCHONDRIA; EXERCISE therapy
- Publication
Science Immunology, 2023, Vol 8, Issue 89, p1
- ISSN
2470-9468
- Publication type
Article
- DOI
10.1126/sciimmunol.adi5377