HnRNPD通过IL-7R调控CD4+T细胞增殖和分化在狼疮性肾炎发病中的作用及其机制研究

CD4+T细胞的增殖和分化失衡是导致狼疮性肾炎(LN)发生发展的关键因素。IL-7R是CD4+T细胞增殖分化的关键，可促进自身反应性CD4+T细胞增殖，同时抑制调节性T（Treg）细胞的功能。本课题组前期研究发现RNA结合蛋白hnRNPD增强IL-7R基因表达，LN患者外周血CD4+T细胞和肾脏组织中hnRNPD和IL-7R表达显著增加，提示hnRNPD可能通过上调IL-7R表达，诱导CD4+T细胞增殖和分化紊乱，导致致病性CD4+T细胞/Treg细胞失衡，肾脏自身免疫性炎症反应加重。为验证这一假说，本项目拟从临床样本、动物及细胞多个层面，阐明hnRNPD通过调控IL-7R对CD4+T细胞增殖分化及LN发生发展的影响及机制。本研究有助于深入理解LN的免疫病理机制，并为LN的治疗策略提供新的线索。

The imbalance of proliferation and differentiation of CD4+T cell is the key factor leading to the development of lupus nephritis (LN). IL-7R plays an important role in the proliferation and differentiation of CD4+T cells. It can promote the proliferation of self reactive CD4+T cells and inhibit the function of regulatory T (Treg) cells. In our previous study, we found that hnRNPD enhanced the expression of IL-7R gene, and the expression of hnRNPD and IL-7R in kidney and CD4+T cells in peripheral blood of LN patients increased significantly, which suggested that hnRNPD might induce the proliferation and differentiation disorder of CD4+T cells through IL-7R, leading to the imbalance of pathogenic CD4+T cells/Treg cells and the aggravation of renal autoimmune inflammatory response. In order to test this hypothesis, this project intends to clarify the effect and mechanism of hnRNPD on the proliferation and differentiation of CD4+T cells and the development of LN, utilising clinical samples, animals and cells model. This study is helpful to understand the immunopathological mechanism of LN and provide new clues for the treatment strategy of LN.