IL-25在炎症性疾病病理中的功能机制

The interleukin 17 (IL-17) family cytokines consist of six members IL-17A-F. IL-17A, also called IL-17, is the most widely investigated member. IL-17 as a pro-inflammatory cytokine plays crucial roles in host defense against microbial infections and in the pathogenesis of inflammatory autoimmune diseases through heterodimer receptors of IL-17RC (a specific receptor) and IL-17RA (a shared receptor of the family). However, the roles of IL-17E, also known as IL-25, are relatively less defined. It has been shown that IL-25 signals through a heterodimeric receptor complex of IL-17RB (a specific receptor) and IL-17RA to induce Th2-associated cytokines and biology. Recently, we have discovered several positive and negative regulation mechanisms in IL-17 mediated signal transduction. Yet, both IL-25 mediated signal transduction and functional mechanisms of this passway in the pathogenesis of inflammatory diseases are largely unknown. This grant is proposed to investigate the IL-25-mediated signaling, screen for new signaling molecules, and demonstrate the functional mechanisms of this pathway in the pathogenesis of inflammatory disease. In addition, the grant also plans to compare the signaling and functional mechanisms of IL-25 with those of IL-17. The goal of this research proposal is to provide new information for targeting strategies for inflammatory diseases.

白细胞介素-17（IL-17）家族，包含IL-17A-F六个细胞因子亚群成员。IL-17A（简称IL-17）是该家族中研究得最清楚的细胞因子，其结合特异性受体IL-17RC和共享受体IL-17RA，在宿主抗感染免疫和自身免疫病的病理中发挥关键作用。然而，IL-17E （也称IL-25）的功能研究相对较少，其通过结合特异性受体IL-17RB和IL-17RA 介导Th2相关生物学功能。我们近期研究阐明了IL-17信号转导中的一些正向与负向调控机制。但IL-25介导的信号通路转导机制研究几乎还是空白，其介导的炎症性疾病过程的机制也不清楚。本申请拟阐明IL-25- IL-17RB通路的信号转导机制，筛选新的信号分子，揭示其在炎症性疾病中的功能与作用机制。同时与IL-17的功能与作用机制做对比，阐明IL-25与IL-17在信号转导及炎症性疾病病理机制中的异同，为炎症相关疾病的治疗奠定扎实的理论基础。