IFNGR2在类风湿关节炎患者Treg/Th17细胞失衡导致骨侵蚀中的作用及机制研究

Treg/Th17 imbalance plays an important role in bone erosion of RA. However, mechanisms of the imbalance are still unknown. IFNγ receptor 2 (IFNGR2) could affect the differentiation of naive CD4+T cells, resulting in the imbalance of T cell subsets. In our previous studies, we found the level of IFNGR2 mRNA was positively correlated with bone erosion in RA. We hypothesize that IFNGR2 may promote bone erosion in RA by inducting Treg/Th17 imbalance. This project intends to explore the mechanisms of Treg/Th17 imbalance induced by IFNGR2 using CD4+T cells through immunomagnetic sorting, plasmid transfection, etc. And further to elucidate whether the inhibition of IFNGR2 function can recover Treg/Th17 balance and reduce bone erosion in rat model of RA. We will investigate the pathologic role and mechanisms of IFNGR2 in bone erosion of RA on the whole, tissue, cell and molecular levels, which may provide a new target for the prevention and treatment of bone erosion in RA.

Treg/Th17细胞失衡在类风湿关节炎（RA）骨侵蚀中起重要作用，但其失衡的机制不详。γ干扰素受体2（IFNGR2）可激活JAK-STAT通路影响初始CD4+T细胞向不同T细胞亚群分化，导致T细胞亚群失衡。我们前期研究发现RA患者外周血IFNGR2 mRNA水平与骨侵蚀呈正相关，因此推测“IFNGR2可能通过诱导Treg/Th17细胞失衡导致RA骨侵蚀”。本课题首先使用离体CD4+T细胞，运用免疫磁珠分选、质粒转染等技术探索IFNGR2诱导Treg/Th17细胞失衡的分子机制，进一步在RA大鼠模型上探讨抑制IFNGR2功能对逆转Treg/Th17失衡并减少骨侵蚀的可能。本课题在整体、组织、细胞及分子水平上全面探讨IFNGR2在RA骨侵蚀中的病理作用及机制，将为RA骨侵蚀的防治提供新的可能治疗靶点。