以iTr35为基础联合Tr1调节系统性硬化症中炎症反应和纤维化病变的作用机制研究

系统性硬化症(SSc)是一种以炎症和纤维化为主要表现的自身免疫性疾病，研究提示Treg细胞在SSc的免疫调节中有重要作用，iTr35是新近鉴定的Treg细胞功能亚群，表型稳定、抑制功能强，可通过免疫调节抑制炎症和纤维化病变达到治疗效果。课题组前期研究发现SSc患者体内存在Th17/Treg失衡，外周血中IL-10诱导的Tr1和IL-35诱导的iTr35存在表型细胞数量，特征性细胞因子的变化，其他的研究亦显示iTr35和Tr1细胞作用具有空间和功能的互补性，可能有内在的相互作用调节自身免疫性疾病的炎症反应。本研究旨在探讨SSc病理过程中iTr35、Tr1细胞及相关因子IL-35和IL-10的表达及动态变化，阐明iTr35细胞调节炎症和纤维化的作用机制，进一步探讨表型稳定的iTr35细胞协同Tr1细胞应用于SSc临床治疗的可能性，这些研究将为为SSc细胞免疫治疗提供理论依据。

Systemic sclerosis (SSc) is a chronic systemic autoimmune disease and is characterized by vasculopathy, inflammation, and fibrosis. Recent studies have suggested that T regulation(Treg) cells play an important role in immune regulation of SSc, iTr35 which is a newly identified functional subgroup of Treg cells, is feature as phenotypic stability and strong inflammation inhibition, and can be regarded as a therapy target through regulating immune to suppress inflammation and fibrosis. Our previous study have demonstrated that Th17/Treg imbalance exists in SSc patients, serum IL-10-induced Tr1 and IL-35-induced iTr35 showed phenotypic cell number and characteristic cytokine changes. And others studies showed that the interactions between iTr35 and Tr1 cells are spatially and functionally complementary and may have intrinsic interactions to regulate the inflammatory response in autoimmune diseases. The study is aiming to investigate the expression and dynamic changes of iTr35, Tr1 cells and related factors IL-35 and IL-10 in the pathogenesis of SSc in order to elucidate the mechanism by which iTr35 cells regulate inflammation and fibrosis. And to explore the possibility of the application of phenotypic stable iTr35 cells in combination with Tr1 cells in SSc therapy, which will provide theoretical basis for the cell immunotherapy in SSc.