缺氧诱导因子-1α调控CD4+T细胞表型及功能参与梗死心脏修复和重塑

CD4+T细胞在梗死心脏中的表型/功能变化及具体调控机制未明。我们前期的RNA-seq分析及部分验证结果提示，和脾脏/非引流淋巴结的CD4+T细胞相比，梗死心脏局部的CD4+T细胞具有疾病特异性的表型和促血管新生功能，且HIF-1α参与CD4+T细胞表型/功能调控。本项目拟进一步①观察梗死心脏中的CD4+T细胞HIF-1α的动态表达规律，验证前期RNA-seq揭示的CD4+T细胞表型/功能变化；②观察去除HIF-1α后对梗死心脏中CD4+T细胞表型/功能的影响及对梗死心脏修复和心室重塑的作用；③在多组学联合分析（RNA-seq和CHIP-seq）的基础上进行功能学验证，深入探索HIF-1α调控梗死心脏中CD4+T细胞表型/功能的分子机理。研究有助于完整阐明梗死心脏中CD4+T细胞的表型/功能变化及调控机制，完善AMI后炎症反应理论，为其干预提供新的靶点。

The phenotypic/function changes and specific regulatory mechanisms of CD4+ T cells in the infarcted heart remain unknown. Our preliminary RNA-seq analysis and validation results suggest that CD4+ T cells in the infarcted heart exhibit a disease-specific phenotype and pro-angiogenic function compared with CD4+ T cells in the lymphoid organs. Hypoxia-inducible factor-1α may regulate the phenotypic/function changes of CD4+ T cells in the infarcted heart. Based on the data, the project intends to①observe the dynamic expression of HIF-1α in CD4+ T cells in the infarcted heart, and completely validate the phenotypic/function changes of CD4+ T cells revealed by RNA-seq; ②observe the influence of inhibiting HIF-1α in CD4+ T cells on its phenotype/function changes and its effects on cardiac repair and ventricular remodeling; ③employ RNA-seq and CHIP-seq to explore the target genes of HIF-1α in CD4+ T cells and validate the regulatory mechanism of HIF-1α on those genes. The project helps to fully elucidate the phenotypic/function changes and regulation mechanisms of CD4+ T cells in infarcted hearts and improve the immune theory for ventricular remodeling, providing new targets for intervention.