APA调控ILCs功能与炎性肠病的研究

固有淋巴细胞（ILCs）在维持肠道黏膜上皮完整性、调节肠道微环境稳态和介导肠道炎症中发挥重要作用。围绕生理和病理过程中ILCs所涉及的信号转导途径、关键转录因子调控及染色质表观遗传修饰等研究已取得重要进展。然而炎性肠病微环境中，ILCs细胞mRNA的选择性多聚腺苷酸化（APA）的整体特征、产生机制及具体生理功能尚缺乏深入研究。因此，本项目拟针对这一重要科学问题，通过各种系统生物学、表观遗传学和分子免疫学等手段，探究病理性肠炎发生发展过程中，ILCs细胞中APA的总体特征，发现参与APA加工的新型蛋白质机器，并阐明其调控ILC功能及炎性肠病进展的机制。本项目的顺利开展，将揭示APA对ILCs分化发育及IBD发生发展的重要调控作用，为炎症性肠病的防治提供靶标和理论基础。

Innate lymphoid cells (ILCs) play an important role in maintaining intestinal epithelial integrity, regulating intestinal microenvironment homeostasis and mediating intestinal inflammation. Significant progress has been made in the study of signal transduction pathways, key transcription factors and epigenetic modification of chromatin involved in the physiological and pathological processes of ILCs. However, in the microenvironment of inflammatory bowel disease, the overall characteristics, production mechanism and specific physiological functions of alternative polyadenylation (APA) of ILCs cell mRNA have not been thoroughly studied. In view of this important scientific problem, this project aims to explore the general characteristics of APA in ILCs cells during the occurrence and development of pathological enteritis by means of various systems biology, epigenetics and molecular immunology, to discover new protein machines involved in APA processing, and to elucidate the mechanism of regulating ILC function and the progress of inflammatory bowel disease. The successful implementation of this project will reveal the important regulatory role of APA in the differentiation and development of ILCs and the occurrence and development of IBD, and provide a target and theoretical basis for the prevention and treatment of inflammatory bowel disease.