IL-21-B10细胞功能轴在ITP发病机制中的作用研究

Primary immune thrombocytopenia (ITP) is considered to be an autoimmune disease, and the loss of immune tolerance plays an important role in the pathogenesis. B10 cells, which have been identified as one of the Breg populations in recent years, play important roles in inhibitory function on inflammation. The B10 cells are involved in immune escape mechanisms of tumor and the pathogenesis of several autoimmune diseases. As a cytokine with multiple function, IL-21 could induce the expansion of B10 cells both in vivo and in vitro. Our previous studies found that the IL-21 levels in ITP patients were significantly higher than in healthy controls while the B10 cells decreased correspondingly, meanwhile the response of B cells from ITP patients to IL-21 showed aberrant. As a result, we speculate the IL-21-B10 cell functional axis in ITP might be anomalous. In this study, we intend to evaluate the level of IL-21 in plasma and the number and function of B10 cells in peripheral blood and spleen, and find the relationship between them. Then we will explore the aberrant mechanism of IL-21 played on B cells activation and differentiation，and B10 cells induction. In addition, we will induce B10 cells by IL-21 and CD40L in vitro, which will provide a theoretical basis of new treatment strategy for the ITP patient.

原发性免疫性血小板减少症（ITP）是一种自身免疫性疾病，免疫失耐受在其发生中扮演了重要角色。B10细胞是近年来发现的一种调节性B细胞，在抑制炎症反应具有重要作用。B10细胞还参与到了肿瘤的免疫逃逸以及多种自身免疫性疾病的发病。IL-21是一种具有多功能的细胞因子，能够在体内和体外诱导B10细胞的扩增。我们之前的研究发现ITP患者IL-21水平升高而B10细胞水平却是降低的，而且ITP患者B细胞对IL-21刺激反应异常，我们推测ITP发病中IL-21-B10细胞功能轴出现紊乱。在本项研究中，我们将检测ITP患者血浆IL-21水平，脾脏和外周B10细胞的比例，并且分析各参数之间的关系。同时研究在IL-21在诱导ITP患者B细胞活化、分化以及诱导B10细胞分化中的异常机制。另外我们还将通过IL-21和CD40L诱导B10细胞的产生，这可能将为ITP的临床治疗提供新的思路

原发性免疫性血小板减少症（ITP）是一种自身免疫性疾病，能够分泌IL-10的调节性B细胞即B10细胞异常在ITP的免疫失耐中扮演了重要角色，而这种B10细胞能够在IL-21的刺激下激活分化，根据既往研究及前期数据我们推测ITP的IL-21-B10细胞功能轴出现紊乱。针对以上现状，我们在本课题中研究了ITP患者IL-21和B10细胞之间的关系，发现二者呈现明显的负相关性；进一步研究了IL-21和B10细胞在免疫细胞活化和诱导分化中起到的作用和相互之间的影响，发现IL-21在能够激活STAT3磷酸化从而诱导B10细胞的产生，但也可以抑制B10细胞发挥免疫调节功能；最后我们从体外通过IL-21和CD40L成功诱导了B10细胞的产生，并且进一步优化诱导条件。本项目揭示了ITP中IL-21和B10细胞功能轴的关系，这可能为体外诱导免疫调节性治疗ITP提供新的思路。