Regular Exercise and the Immune System

Regular exercise is well-known to have many health benefits, including protecting against cardiovascular disease, reducing the risk of diabetes, and shielding against declining cognitive abilities. The precise mechanisms behind these benefits have long puzzled scientists. A new study by Langston et al, contributes to the ongoing efforts to understand the cellular and molecular changes of exercise, focusing on the immune system activity within the muscle tissue. The study highlights how the immune system plays an important role in tissue health during exercise.

The authors developed an acute and chronic exercise model to mimic acute versus regular exercise training. Langston et al, found that both models induced muscle inflammation including IFN signaling which directly impairs muscle mitochondria function. Also, regulatory T cells (Tregs) which are immune cells known for countering inflammation were recruited to the muscle after both acute and chronic exercise. In addition, both models, also increase activity of genes that regulate different metabolic processes including glycogen metabolism, muscle structure and wound-healing responses. While both exercise models recruited Tregs, only the chronic exercise group benefited metabolically by muscle energy usage and endurance. To investigate whether Tregs are important for the beneficial effects of exercise, the authors focused on the chronic exercise model because the improvements in metabolism and endurance associated with exercise require weeks of regular training.

To validate the role of Tregs in controlling exercised-induced inflammation and promoting beneficial effects, the researchers depleted Tregs in mice and expose them to chronic exercise. Animals that lacked Tregs had uncontrolled muscle inflammation mediated by increased interferon levels and decreased adaptation to exercise over time. 

These findings highlight the cellular mechanisms underlying exercise's anti-inflammatory effects via Tregs and emphasize the potential of harnessing the body's immune system through physical activity. Tregs have garnered attention as potential targets for therapies aimed at reducing inflammation, while exercise offers a natural means to enhance immune responses and counter inflammation throughout the body.  

Tregs continue to be targeted for immune-mediated diseases and this study emphasizes the role of exercise in reducing inflammation and boosting immune responses.

About the main author: Kent Langston is a postdoctoral fellow in the lab of Diane Mathis and Christophe Benoist at Harvard Medical School. His research interests include cellular immunology, immunometabolism, skeletal muscle biology, and mitochondrial physiology. 

Original Research Article:

Langston, P. K., Sun, Y., Ryback, B. A., Mueller, A. L., Spiegelman, B. M., Benoist, C., & Mathis, D. (2023). Regulatory T cells shield muscle mitochondria from interferon-γ-mediated damage to promote the beneficial effects of exercise. Science immunology, 8(89), eadi5377.

https://news.harvard.edu/gazette/story/2023/11/new-study-explains-how-exercise-reduces-chronic-inflammation/