固有免疫细胞的活化有关免疫反应的有效启动与维持，其活化失调与感染、炎症、自身免疫病等多种疾病相关。课题组在前期的研究中发现，固有免疫细胞中高表达的PRL2分子，在炎症环境与氧化压力下，蛋白水平会显著下调。通过构建PRL2全身敲除与髓系固有免疫细胞条件性敲除小鼠，我们发现PRL2缺失的小鼠抵抗细菌感染的能力明显增强，细胞产生ROS与杀伤细菌的能力显著提高，提示PRL2可通过调控ROS的产生在抗菌感染免疫中发挥作用。进一步的研究发现，PRL2可与Rac GTPase以及TIPE2分子结合，鉴于两者为免疫细胞活化调控的重要分子，本课题将以此为切入点，对PRL2调控固有免疫细胞活化的分子机制进行深入探索，并在细胞与动物水平，对该分子及其相关信号通路在免疫细胞代谢、生存分化、移行、吞噬杀伤以及体内抗菌感染免疫中的作用进行研究。

The activation of innate immune cells has an important role in initiating and maintaining immune responses. Dysregulation of the innate immune response is associated infectious diseases, inflammation, and autoimmune diseases. We found PRL2 (phosphatase regenerating liver 2) is highly expressed in resting immune cells, but is markedly downregulated by inflammation and oxidative stress. Using PRL2 total knockout and myeloid cell conditional knockout mice, we found PRL2 knockout mice were resistant to bacterial infection. PRL2 deficient innate immune cells produced more ROS and exhibited enhanced bactericidal activity. PRL2 binds with Rac GTPase and TIPE2, which are key regulatory molecules in innate immune responses. In this project, we are going to study molecular mechanisms of PRL2 in activation of innate immune cells. We will study roles of PRL2 in innate immune cell metabolism, survival, differentiation, migration, phagocytosis, as well as antibacterial responses in vivo.