Rho小G蛋白亚家族既可以通过动态调节肌动蛋白细胞骨架调控细胞形态、运动和粘附,也可通过调节基因表达影响细胞增殖和免疫应答。Rho小G蛋白Rif是否能参与免疫应答未有相关报道。本申请人前期研究发现Rif在免疫细胞中特异性高表达，并可以促进NF-κB信号通路激活，表明其可能在免疫应答中发挥重要功能。本项目拟运用Rif组成型基因敲除小鼠及细胞模型，揭示Rif在模式识别受体介导的固有免疫应答中的作用，阐明Rif对树突状细胞成熟、迁移及诱导CD8+T细胞适应性免疫应答的调控机制。本研究首次将GTP酶Rif与病原细菌感染下模式识别受体介导的固有免疫应答以及树突状细胞诱导的T细胞免疫应答联系起来，其研究成果将揭示真核细胞拮抗病原微生物感染的新信号转导通路，加深对于感染和致病分子机理的理解。

The Rho subfamily of small G proteins plays critical roles in cell morphology, movement, and adhesion by dynamic regulation of actin cytoskeleton. In the meanwhile, they can also affect cell proliferation and immune responses by regulating gene expression. It is known that the small Rho GTPase Rif (Rho in filopodia) can regulate the formation of filopodia structure, but it is still unclear whether it can participate in the intracellular immune regulation processes. We found that Rif displays a restricted expression pattern in immune cells, indicating its potential function in immune response. It further revealed that Rif can promote the activation of NF-κB. Based on the results obtained, the study has been designed to investigate the regulation mechanisms of the small GTPase Rif on innate and adaptive immune responses. In this grant application, we will employ constitutive Rif-/- genetic mice and cell line models to reveal roles of Rif in pattern recognition receptors (PRRs)-mediated innate immune response, and to elucidate the regulatory mechanism of Rif on dendritic cell (DC) maturation, migration and induction of CD8+ T cell responses. These studies link Rif to PRRs mediated innate immune responses and DC induced CD8+ T cell responses for the first time, which can uncover novel signaling pathways to against pathogen infection.