[Advances in the molecular mechanisms of subtle mechanical forces in immune regulation]

Subtle mechanical forces (such as cellular stretching, shear stress, tissue pressure, ultrasound, and acupuncture, which are lower than the tissue and cell damage thresholds but can be sensed and transduced by cells) can regulate the physiological functions of immune cells through mechanosensitive ion channels (MSCs). When being sensed by MSCs on the surface of immune cells, these subtle mechanical stimuli are converted into biochemical signals that trigger cellular activation, migration, phagocytosis, and cytokine release. Under pathological conditions such as inflammation, infection, and cancer, mechanical signals are transmitted through mechanosensitive channels-including Piezo, TRPV, MRTFA-SRF, Hippo-YAP/TAZ, and integrins-to modulate both innate and adaptive immune responses. The "subtle mechanical force-MSC-immunity" axis plays a crucial role in inflammation modulation, pathogen clearance, and antitumor immunity, holding significant potential for translational applications. This review summarizes the mechanisms by which subtle mechanical forces mediate immune modulation through MSCs and outlines the functions and signal transduction mechanisms of subtle mechanical forces and MSCs, with a particular focus on the roles of Piezo, TRPV, MRTFA-SRF, Hippo-YAP/TAZ, and integrin channels in various immune cells. It further elaborates on the immunomodulatory effects and the potential application prospects of exogenous subtle mechanical stimuli in physical therapy, aiming to provide new insights for understanding the regulation of immune responses by subtle mechanical forces and offer a theoretical basis for developing novel immunotherapies based on subtle mechanical forces.