组蛋白去乙酰化酶3在铜绿假单胞菌肺炎发病中的作用及其机制

巨噬细胞作为一类重要的天然免疫细胞，在炎症反应和细菌清除中起着重要作用。组蛋白去乙酰化酶（HDAC3）通过移除靶蛋白的乙酰化基团，影响蛋白的结构和功能。相较于野生型细胞，Hdac3基因敲除巨噬细胞的炎症因子表达和抗原提呈能力受到明显抑制。将内毒素脂多糖（LPS）刺激前后的巨噬细胞行RNAseq及信号通路富集，发现Hdac3缺失影响一系列炎症信号通路的活化，包括NF-kB，JAK/STAT等。本课题拟继续开展如下研究：（1）利用Hdac3巨噬细胞条件敲除性小鼠，培养骨髓来源的巨噬细胞，检测铜绿假单胞菌或LPS刺激后细胞表型及功能的变化；（2）通过Hdac3巨噬细胞条件敲除性小鼠建立铜绿假单胞菌性肺炎模型，进一步阐明HDAC3在炎症反应和细菌清除中的作用。本研究将为细菌性肺炎的免疫学治疗提供新的思路和手段。

As a class of innate immune cells, macrophages play an important role in inflammatory response and bacterial clearance. Histone deacetylase (HDAC)3 affects the structure and function of the protein by removing its acetylated group. Compared with wild-type cells, the inflammatory factor levels and the antigen-presenting ability of Hdac3 knockout macrophages were significantly inhibited. RNAseq and signal pathway enrichment results before or after lipopolysaccharide (LPS) stimulation indicated that the absence of HDAC3 in macrophages affected the activation of a series of inflammation related signalling pathways，including NF-kB, MAPK, JAK/STAT, et al. Our following research plans include: (1) Culture bone marrow-derived macrophages from Hadc3 macrophage knockout mice and detect the changes of cell phenotype and function after stimulation by Pseudomonas aeruginosa or LPS; (2) Establish a mouse model of Pseudomonas aeruginosa pneumonia through macrophage Hdac3 knockout mice to further clarify the role of HDAC3 in inflammatory response and bacterial clearance. Our study will provide new ideas and methods for the immunotherapy of bacterial pneumonia.