Emerging Mechanistic Insights into How Physical Activity Shapes Immune Cell Function

Abstract

Regular physical activity represents a robust, non-pharmacological means of tuning immune function. In this review, we outline the multi-layered molecular logic through which exercise reshapes immunity. At the level of cell positioning, exercise dynamically calibrates chemokine networks to steer immune-cell migration in both directions, enabling a precise balance between anti-inflammatory control and tissue repair. In parallel, exercise induces metabolic reprogramming that promotes macrophage polarization toward anti-inflammatory states and, in doing so, can imprint a form of metabolically conditioned immune memory. Meanwhile, by reconfiguring core signalling hubs—including MAPK, NF-κB and cGAS–STING—exercise contributes to an immune microenvironment that favours physiological homeostasis. Notably, metabolites generated or accumulated during exercise, such as lactate and β-hydroxybutyrate, can further act through epigenetic mechanisms, exerting sustained influence on immune-cell programmes. Beyond peripheral immune regulation, exercise also modulates systemic immunity by shaping bone-marrow haematopoiesis and dampening the progression of immunosenescence, thereby refining immune status with greater precision. Taken together, these convergent mechanisms provide a coherent scientific basis for exercise-mediated maintenance of immune homeostasis, offering conceptual support for disease prevention strategies and the design of personalized exercise prescriptions. Looking ahead, deeper integration of immune features in Chinese populations with perspectives from traditional medical thought may help drive a more locally grounded, translational agenda in exercise immunology.