The Hippo signaling pathway regulates cell proliferation,organ size and tissue regeneration through a series of kinase cascades.MST1/2 is the mammalian orthologue of the core kinase Hippo,which is crucial for the activation of downstream signaling.Additionally,MST1/2 has been reported to play important roles in cell differentiation,morphology and cytoskeleton reorganization.Recent evidence suggests that MST1/2 is involved in the regulation of T cell adhesion,migration,homing and Treg cell maturation and functions.Interestingly,these processes are not dependent on the canonical,but a non-canonical Hippo signaling pathway.More recent studies have revealed that MST1/2 mediates the innate immune response against pathogens or viruses,especially on macrophage phagocytosis as well as cytokines and ROS production.MST1/2 is associated with various diseases,such as bacterial or viral infection,inflammation-related cancer,and atherosclerosis.In this review,we summarize recent findings on the functions of MST1/2 in the innate immune response and inflammation-related diseases.%Hippo信号通路通过一系列激酶级联反应,实现对细胞增殖、器官大小以及组织再生等方面的调控.其中,MST1/2是核心激酶Hippo蛋白在哺乳动物中的同源物,对于下游信号通路的激活至关重要.此外,MST1/2在细胞分化、形态和细胞骨架重排等方面也发挥重要作用.近期多项研究工作指出,MST1/2参与调控免疫T细胞的粘附、迁移、归巢和抑制性Treg细胞的成熟与功能,以及心肌细胞自噬等过程.有趣的是,这一功能是不依赖经典的Hippo信号通路的,被称为“非经典Hippo信号通路”.最新的研究结果揭示了MST1/2通过非经典Hippo信号通路调控先天免疫巨噬细胞对病原菌或病毒的免疫应答,包括巨噬细胞的吞噬、细胞因子(炎症因子、趋化因子、I型干扰素等)和线粒体活性氧的产生,从而在机体抵抗细菌病毒感染、炎症相关癌症、动脉粥样硬化等疾病中发挥重要功能.本文对MST1/2调控先天免疫功能、相关分子机制和疾病进行了总结和讨论.
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