接头蛋白BCAP通过调控PI3K、NF-κB等信号通路，分别在巨噬、NK和B细胞的分化和免疫应答中起到细胞特异性的调控作用。虽然T细胞不表达BCAP，但BCAP-KO小鼠中效应T细胞增多，提示BCAP可能通过调节树突状细胞（DC）的成熟活化，影响了T细胞的分化，而BCAP在DC中的作用却仍一无所知。本实验室前期研究发现，BCAP-KO小鼠体液免疫减弱，炎症反应增强；老龄化小鼠脏器有明显炎症；BCAP-KO BMDC的成熟分化表型和功能异常。体外实验发现，BCAP可同时开启及反馈调节NF-κB和PI3K信号通路；同时，对Toll样受体介导的免疫应答表现出以MyD88依赖和非依赖为区别的差异反应。据此，本项目拟以DC特异性BCAP缺陷小鼠为模型，深入研究BCAP在DC前体细胞分化发育及活化成熟中的作用和机制，特别是对不同诱导因子来源信号通路的差异反应，及维持DC免疫应答过程中稳态的作用和机制。

The adaptor protein BCAP involves in regulating the development and function of macrophage, NK cell and B cell. Notably, BCAP regulates distinct signaling pathways in different cell types, suggesting that it exerts a cell-specific further. Intriguingly, although T cell doesn’t express BCAP protein, the proportion of effector/memory T cells in the BCAP-KO resting mice is higher than wild-type mice. This indicates that BCAP may indirectly affect T cell function via regulating DC maturation. Our previous study demonstrated that BCAP-KO mice had attenuated humoral immune response and increased inflammation-obvious inflammation in the organ of aged BCAP-KO mice. What’s more, we also found that BCAP is involved in regulating DC maturation including phenotype and function. It inhibited and feedback regulated the NF-κB and PI3K pathway through the dynamic interaction with MyD88. While, on the other hand, BCAP showed another function model in the MyD88-independent signal pathway, which suggests that in the MyD88-dependent or –independent signals, BCAP functions as a selector to regulate different pathways. In this study, the effects of BCAP regulating signaling pathways and its functions on DC development and immune responses will be further investigated; especially the mechanisms of selective regulation of signals and maintaining the homeostasis in DC response to immune stimulus.