抗原提呈细胞分化发育功能调控及参与炎症性自身免疫性疾病的表观遗传机制研究

表观遗传修饰是以DNA甲基化、组蛋白修饰及非编码RNA为核心，在不同层次相互作用和整合，实现对基因转录和转录后调节。表观机制对免疫细胞分化发育和功能调节至关重要。树突状细胞、巨噬细胞作为专职性抗原提呈细胞APC在免疫应答与免疫病理中具有独特地位，但目前对其分化和功能调控表观机制尚不清晰。本课题组以表观组学体系，获得了人和小鼠树突状细胞、巨噬细胞不同分化成熟阶段的全基因组DNA甲基化谱、组蛋白修饰谱、表达谱及microRNA组的数据，拟在此基础上，深入寻找和分析调控APC分化成熟、功能特征和应答功能差异表观修饰位点，结合炎症性自身免疫性疾病等模型，系统研究表观调控因子在APC免疫识别和应答过程中的动态调控网络，揭示这些表观修饰位点在调控APC分化成熟及维持其特异性功能状态中的关键作用，探索免疫细胞功能调控和免疫识别与应答的新机制，提出免疫表观调控的新观点。

Sets of epigenetic information such as DNA methylation, histone modification and non-coding RNA which constitute additional layers of transcription regulation have been discovered to play key roles in setting up and maintaining unique cell identity during eukaryotes development and differentiation. Epigenetic regulatory mechanisms are a central element in immune cell differentiation and function, allowing a specific gene expression pattern for lineage commitment and appropriate immune responses. From the point of view of epigenome, systematically analyzing genome-wide chromatin modifications provides powerful tools for data-based immunological research. Recently, more and more DNA methylomes and histone modifications in T and B cells have been widely revealed through microarray and deep sequencing combined with traditional epigenetic techniques such as bisulfite PCR and Chromatin IP (ChIP). But epigenetic regulation of antigen presenting cells including dendritic cells and macrophages are less reported. Through epigenomic techniques, we have obtained the profiles of DNA methylation, histone modification, transcriptome and miRNome during the differentiation and maturation of DCs and macrophages both in human and mice. In this project we intend to study the dynamic profiles of DNA methylation, histone modification, transcriptome and miRNome for DCs and macrophages, aiming to further discovery of epigenetic regulators in APC differentiation and maturation and reveal the significance of epigenetic regulators in the inflammatory autoimmune disease models. It will provide us with a way to mining key epigenetic regulator for identity and function of DCs, macrophages and outline new clues to study the pathogenesis of immunological disorders.