Research Progress in the Molecular Mechanisms of Exercise-Mediated Immunoregulation

Regular exercise is recognized as an effective strategy for preventing and managing inflammatory, metabolic, and autoimmune diseases, as well as malignancies. These benefits are largely mediated through the immune system via a multi-level regulatory network. On one hand, exercise modulates immune responses through mechanisms such as mechanical stress sensing, neuroendocrine regulation, and metabolic reprogramming. On the other hand, exerkines—such as IL-6 and irisin—released by skeletal muscle and other tissues, cooperate with the remodeled gut microbiota to form a cross-organ signaling network. These signals exert bidirectional immunomodulatory effects by guiding immune cell chemotaxis and migration, reprogramming cellular metabolic patterns, regulating key immune-related pathways, and inducing epigenetic modifications. As a result, exercise promotes an anti-inflammatory phenotype in chronic inflammatory conditions while enhancing immune surveillance in the tumor microenvironment. This review systematically elucidates the molecular mechanisms by which exercise regulates the immune system, providing a theoretical foundation for translating basic research in exercise immunology into clinical practice.