Transitional型B淋巴细胞及其亚群IL-6/IL-10功能轴稳态失衡参与ITP发病机制的研究

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。我们的前期研究提示 ITP 患者 PTEN 的异常表达可能在 ITP 的transitional B细胞亚群稳态失衡中发挥作用，我们推测其可能导致胞内的细胞因子平衡紊乱，使得自身反应性B细胞大量出现在外周血。在本项目研究中，我们将进一步明确 transitional B细胞亚群的功能是否异常，通过检测胞内IL-6/IL-10及相关信号通路，阐明transitional B细胞异常的内在缺陷。最终我们将揭示具备自身反应潜能的transitional B细胞亚群如何逃阴性选择并向分泌抗血小板抗体的浆细胞分化参与ITP的发病，为ITP的临床治疗提供新的思路与靶点。

Primary immune thrombocytopenia (ITP) is considered to be an autoimmune disease, and the loss of immune tolerance plays an important role in the pathogenesis.Our previous studies suggested that defective PTEN expression play a role in homeostasis of transitional B cells and their subsets.We hypothesized that imbalance of the cytokines homeostasis causing auto-reactive B cells are abundantly present in peripheral blood. In our study ,we will systematically describe the phenotypic and functional characteristics of transitional B cell subsets in ITP.Furthermore,we will examined the cellular cytokines of IL-6/IL-10 and intracellular signaling to explore the molecular mechanisms of abnormal transitional B cells.Finally,our study will elucidate the mechanisms that Self-tolerance breakdown contributes to differentiation and expansion, activation and survival of transitional B cell subsets in ITP,which will provide a theoretical basis of new treatment strategy for the ITP patient.