I型干扰素和促炎性细胞因子在宿主抵抗病原微生物感染中发挥关键作用，但异常表达可导致自身免疫病、炎性疾病和肿瘤的发生。申请人以病毒感染为模型，围绕天然免疫的信号转导进行了系统的研究，发现TRIP、TRIM26/38、USP4/2b等多个调控I型干扰素表达和抗病毒免疫反应的调节因子，为在分子水平诠释抗病毒天然免疫信号转导及其调控机制做出了创新性贡献；发现TRIM38、miR-210等调控促炎性细胞因子表达的机制，为解析炎症反应的调控机理提供了新的线索。作为通讯/共同通讯作者发表SCI论文16篇，已被Nat Immunol、Immunity、Annu Rev Immunol等SCI期刊他引188次。获聘山东省感染与免疫重点实验室主任，山东省“泰山学者”特聘教授。未来几年中，将在分子、细胞和动物整体水平，深入研究蛋白质泛素化修饰在抗感染天然免疫中的调控作用，完善抗病毒天然免疫的调控网络。

Type I inteferons and proinflammatory cytokines produced by the innate immune system play essential roles for the host to prevent bacterial and viral infection. At the same time, these cytokines are also important to maintain the immune homeostasis because aberrant expression of these cytokines could lead to the occurrence of autoimmune diseases, inflammatory diseases and cancer. Virus infection leads to the production of type I inteferons and proinflammatory cytokines. During the last several years, the applicant has used virus infection as a model system to study the molecular mechanisms involved in the production of type I inteferons and proinflammatory cytokines. The applicant has identified TRIP, TRIM26/38, USP4/2b as critical regulatory molecules in the regulation of virus-triggered innate signaling and production of type I inteferons. The applicant also revealed roles of TRIM38, hnRNP U and miR-210 in the production of proinflammatory cytokines. Mechanistically, these regulators exert their function on various molecules in the antiviral signaling pathways to regulate the antiviral innate immune responses and inflammation. Part of the results has been published in the Journal of Experimental Medicine, PLOS Pathogens, the Journal of Immunology, Journal of Virology and the Journal of Biological Chemistry et al. After publication, these papers have been cited as many as 188 times by other prestigious peer-reviewed journals including Nature Immunology, Immunity, Annual Review of Immunology, Annual Review of Physiology, Trends in Immunology and Current Opinion in Immunology et al. The applicant was awarded the professorship of Taishan Scholar by the Shandong Province in 2007. Now, the applicant serves as the director of the key laboratory of immunity and infection of Shandong Province. In this following proposal, the applicant will mainly use animal models to identify more E3 ligases and DUBs that regulate antiviral innate immune response and inflammation.