转录因⼦ThPOK在III型固有淋巴细胞（ILC3）中的功能机制研究

固有淋巴细胞（ILCs）是一种固有免疫细胞，同时具有分泌细胞因子等获得性免疫的相关功能，使得其成为固有免疫与适应性免疫间交流的重要桥梁。作为T淋巴细胞亚群的“镜像细胞”，ILCs分泌的细胞因子和关键调控的转录因子，都与T细胞表现出一定的相似性，但也具有一定的独特性。转录因子ThPOK属于POK/ZBTB蛋白家族成员,是胸腺细胞谱系发育过程中的决定因素，但在固有淋巴细胞中的作用还未有详尽研究。申请人前期研究发现，小鼠肠道不同ILCs亚群中，ILC3表达较高水平ThPOK。敲除ThPOK后ILCs前体细胞的发育未受影响，但ILC3重新表达CD8。同时小鼠炎症性肠炎模型表明ThPOK可通过调控IL-17A的分泌参与肠道稳态的维持。因此本课题接下来将会通过RNA-seq和CHIP进一步探明ThPOK在ILC3中作用的具体分子机制，为临床治疗炎症性肠病提供理论基础。

Innate lymphoid cells (ILCs) are a kind of innate immune cells, and they also have the function of secreting cytokines and other acquired immunity, making them an important bridge for communication between innate immunity and adaptive immunity. As the "mirror cells" of T lymphocyte subsets, the cytokines secreted by ILCs and the key regulatory transcription factors all show certain similarities to T cells, but they also have certain uniqueness. The transcription factor ThPOK is a member of the POK/ZBTB protein family and is a decisive factor in the development of the thymocyte lineage, but its role in innate lymphocytes has not been studied in detail. The applicant’s previous research found that in different subgroups of ILCs in the intestine of mice, ILC3 expressed higher levels of ThPOK. The development of ILCs precursor cells was not affected after ThPOK was knocked out, but ILC3 expressed CD8 again. At the same time, the mouse model of inflammatory bowel disease shows that ThPOK can participate in the maintenance of intestinal homeostasis by regulating the secretion of IL-17A. Therefore, this project will further explore the specific molecular mechanism of ThPOK in ILC3 through RNA-seq and CHIP, and provide a theoretical basis for clinical treatment of inflammatory bowel disease.