免疫性血小板减少症（ITP）是一种最常见的获得性自身免疫性出血性疾病，其发病与血小板自身抗体介导的血小板损伤与破坏有关，然而血小板自身抗体产生的具体机制在ITP中尚不明确。研究表明，滤泡辅助性T（Tfh）细胞在自身抗体的产生中起重要作用。本项目组前期研究发现，Tfh2细胞极可能是促使ITP患者B细胞产生血小板自身抗体最主要的Tfh细胞亚群。但是，Tfh2细胞的分化受到哪些上游分子的调控进而诱发ITP尚不清楚。本项目拟在已有基础上探讨OX40L/OX40轴对naive CD4+T细胞向Tfh2细胞分化的调节作用，并进一步分析Tfh2细胞辅助B细胞产生血小板自身抗体进而介导ITP发生发展的分子机制。本项目预期结果将从OX40L/OX40信号轴这个新视角揭示Tfh2细胞介导血小板自身抗体产生的分子机制，并探讨OX40L和OX40分子作为潜在的临床生物标志物的价值，为ITP防治提供新思路。

Immune thrombocytopenia (ITP) is one of the most common acquired autoimmune hemorrhagic diseases, which is related to platelet injury and destruction mediated by platelet autoantibodies. However, the specific mechanism of platelet autoantibodies production is unclear in the pathogenesis of ITP. Studies have shown that follicular helper T (Tfh) cells play an important role in the generation of autoantibodies. Previous studies of our team found that Tfh2 cells were likely to be the most important Tfh cell subsets that promote the production of platelet autoantibodies by B cells in ITP patients. However, it is not clear that which upstream molecules regulate the differentiation of Tfh2 cells and further induce ITP. Taken together, the purpose of this study was to investigate the regulatory role of OX40L/OX40 axis on the differentiation of naive CD4+T cells into Tfh2 cells, and to further analyze the molecular mechanism of Tfh2 cells assisting B cells to produce platelet autoantibodies that mediate the initiation and development of ITP. The expected results of this project will reveal the molecular mechanism of platelet autoantibodies production mediated by Tfh2 cells from the novel viewpoint of OX40L/OX40 signal axis, and explore the value of OX40L and OX40 molecules as potential clinical biomarkers, and provide new insight for the prevention and treatment of ITP.