蛋白酶体激活蛋白 REGγ 在固有免疫和宿主防御中的作用以及机制研究

败血症作为一类系统性免疫失调疾病严重威胁着人类的生存与健康。在败血症的发生过程中，机体的固有免疫系统发挥着重要的调控作用。尽管泛素-蛋白酶体途径在免疫系统中的重要作用已被广泛认可，但是非泛素依赖的蛋白酶体在免疫系统中的作用却知之甚少。本项目前期通过小鼠败血症与细菌感染模型发现：非泛素依赖蛋白酶体激活蛋白REGγ在小鼠细菌感染及败血症的发生中有重要的调控作用。本项目拟进一步研究REGγ在巨噬细胞、中性粒细胞中的生物功能以及REGγ调控吞噬细胞杀菌能力的分子机制，另外，我们也将研究REGγ本身在细菌感染过程中表达调控的分子机制，以期能阐明非泛素依赖的蛋白酶体在免疫系统所起到的作用，为败血症的治疗找到新的靶点。

Sepsis is known as a systemic, deleterious host response to infection threatening peoples’ health and innate immunity plays a direct role in the development of sepsis. Ubiquitin-dependent proteasome system is widely studied in immune system and is proved to play an important role in immune regulation, whereas, the role of ubiquitin-independent pathway in immunity remains unknown. From the previous work, We demonstrate that REGγ may function as a key regulator of host defense against bacterial pathogens. Furthermore, the expression of REGγ is also regulated during bacterial infections. Based on these findings, we plan to clarify detailed mechanism of REGγ in regulating host defense against bacterial infections and to prove that REGγ may be a potential target in treatment of sepsis.