机械力在免疫调节中的信号传导机制研究进展

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

摘要:

机械力(如细胞牵张、剪切力、组织压力、超声波及针刺等低于组织和细胞结构损伤阈值、但足以被细胞感知并转导的物理刺激)可通过机械力敏感离子通道(mechanosensitive ion channel, MSCs)调控免疫细胞的生理功能。当机械力被免疫细胞表面的机械力敏感离子通道感知后，可将其转化为生化信号，从而触发免疫细胞的激活、迁移、吞噬和炎症因子释放等。在炎症、感染、肿瘤等疾病状态下，机械信号通过Piezo、TRPV、MRTFA-SRF和Hippo-YAP/TAZ通路以及整合素等机械敏感通道影响先天和适应性免疫反应。“机械力-机械力敏感离子通道-免疫”轴在炎症调控、病原清除和抗肿瘤免疫中发挥重要作用，具有显著的临床应用前景。本文综述了机械力通过机械力敏感离子通道介导的免疫调节机制，概述了机械力与机械力敏感离子通道的功能与信号传导机制，进一步阐述了机械力敏感离子通道在不同免疫细胞(T细胞、巨噬细胞、树突状细胞及肥大细胞)中的作用，分析了“机械力-机械敏感通道-免疫”轴在炎症等疾病中的免疫调控效应，并探讨了物理疗法中外源微弱机械刺激的免疫调节作用及其潜在应用前景。本文为理解机械力调控免疫反应提供了新思路，并为基于机械力的新型免疫疗法提供了理论基础。

Abstract:

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.