P. Kent Langston, PhD

Using a multimodal experimental approach, we demonstrated that appropriate regulation of physiological inflammation by regulatory T cells (Tregs) is required for the muscle-specific and organism-level metabolic adaptations and improved performance typical of exercise training (Langston et al. 2023. Science Immunology). Notably, this was the first study in which an immunocyte subset was punctually ablated to assess its importance in exercise adaptation. We identified interferon gamma as a T-cell and NK-cell effector molecule that is unleashed in Treg-deficient mice and is necessary and sufficient to impair muscle mitochondrial function to the detriment of endurance-exercise performance. The profound defects in exercise adaptation, at the muscle level and systemically, caused by excessive inflammatory responses prompted us to ask why exercise induces muscle inflammation at all – i.e., how non-parenchymal cells in muscle sense exercise. Interestingly, we found that muscle mesenchymal stromal cells (MmSCs), also commonly called fibroadipogenic progenitors, sense exercise-induced changes in the mechanical properties of muscle via the mechanosensitive ion channel Piezo1 (Langston et al. 2026. Nature Immunology). Such mechanosensation triggers an inflammatory reaction among MmSCs, which is characterized by their upregulation of many immunomodulatory factors, including IL-6 and CCL2. Notably, this response was site-specific, occurring only in muscles that exhibited changes in stiffness in response to exercise (i.e., gastrocnemius and quadriceps, not tibialis anterior), and was necessary for consequent recruitment of leukocytes to muscle. A similar reaction also occurs in injured and aged muscles, nominating mechanosensing as a potential target for anti-inflammatory therapies for these conditions.

The Langston laboratory aims to characterize the immunometabolic drivers of exercise adaptation and muscle aging. We are a growing interdisciplinary team that values creativity and collaboration. If you are interested in muscle immunobiology and/or bioengineering, please do not hesitate to reach out.