蛋白激酶Stk38对树突状细胞IL-12的产生和Th1型抗结核免疫反应的调节作用

树突状细胞作为功能最强大的抗原递呈细胞，不仅广泛参与炎症、抗感染及抗肿瘤免疫反应，在获得性免疫应答方面也发挥重要调控功能。DC模式识别受体信号传导对DC功能的发挥具有重要的调控作用，但对DC模式识别信号转导机制的研究开展得较少。蛋白激酶Stk38是Hippo信号通路中重要的信号分子，我们此前的研究发现Stk38抑制巨噬细胞TLR9介导的天然炎症反应（Nat Commun.，2015），但在后续实验中我们发现Stk38促进DC和巨噬细胞中CpG、LPS诱导的IL-12的产生并促进T细胞中IFN-gamma的产生。因此，我们拟开展Stk38在DC的生物学功能调控和获得性免疫应答调控的相关研究，同时利用小鼠结核疾病模型，探讨Stk38可能的调控作用，并进一步探讨其分子机制。通过本课题研究，旨在发现Stk38调控免疫反应的新功能和新的作用机理，并为相关免疫疾病提供新的发病机理解释和潜在的治疗靶点。

Dendritic cells, as the most powerful antigen-presentation cell, play important roles in both innate and adaptive immunity. PRR signaling regulates the function of DCs, however, the mechanism of PRR signaling in DCs remains largely unknown. Protein kinase Stk38, a highly conservative evolution member of serine/threonine-protein kinase family NDR/LATS, extensively participates in cell cycle, cell apoptosis, cell differentiation, autophagy regulation and tumorigenesis etc. Our primary results show that Stk38 increases CpG- and LPS-induced IL-12 production in DCs. So, we plan to explore the regulatory role of Stk38 in the function of DCs in adaptive immune response. Meanwhile, we will further explore the possible role of Stk38 in mice tuberculosis model. Our study may identify the new and key function and mechanism of Stk38 in immune regulation, and possibly provide new mechanistic explanations or potent therapeutical target for related immune disease.