IL-17B调控肠粘膜巨噬细胞极化在溃疡性结肠炎中的保护作用机制研究

The polarization of M1/M2 macrophage plays an important role in the pathogenesis of Ulcer colitis (UC). The cytokines regulating macrophage polarization might be the new methods for UC therapy. IL-17B is recently identified to play a protective role in UC development. Preliminary data showed that IL-17B negative regulating M1 cells, but the mechanism is unknown. We hypothesize that IL-17B could inhibit M1 polarization by regulating JAK-STAT signaling, playing an important role in UC development. In this project, we will regulate IL-17B expression in DSS-colitis model and study the M1/M2 macrophage infiltration in the gut mucosa, JAK-STAT signaling activation, and UC pathology. Then we will regulate JAK-STAT pathway to see how IL-17B regulates M1/M2 polarization. The aim is to study whether IL-17B modulate macrophage polarization by regulating JAK-STAT signaling to protect UC development. This project will better our understanding of the mechanism of UC and make IL-17B to be a novel cytokine to UC therapy.

肠黏膜M1/M2巨噬细胞极化对UC的发生具有重要作用，有效抑制M1巨噬细胞极化的细胞因子可做为UC治疗的新型免疫调节因子。IL-17B是新近发现的具有抑制肠黏膜炎症反应的新型细胞因子，前期实验显示IL-17B可负调控M1细胞功能，但机制尚不清楚。初步研究显示IL-17B可抑制JAK-STAT1的激活，并激活STAT6，我们推测IL-17B可调控巨噬细胞JAK-STAT信号通路，负调控M1细胞极化在UC发生中起保护效应。本项目以DSS诱导的结肠炎为模型，调控IL-17B的功能，研究黏膜巨噬细胞极化、JAK-STAT信号通路激活及UC病变的关系；调控JAK-STAT信号通路，研究IL-17B对M1/M2细胞极化的影响，探讨IL-17B 通过JAK-STAT信号调控肠黏膜巨噬细胞极化在UC发生中的保护作用，为深入理解UC的发病机制，使IL-17B做为新型免疫调节因子用于UC治疗提供理论支撑。