2型固有淋巴细胞促进心梗后心肌纤维化的作用及其活化的调控机制研究

心肌纤维化是心梗后心肌重构和心力衰竭的主要因素，其中免疫反应发挥关键作用。研究证实，2型固有淋巴细胞（ILC2）活化能介导组织纤维化。我们前期研究发现，清除ILC2的小鼠，心梗后心肌纤维化明显减轻，证明ILC2的活化能介导心肌纤维化，但ILC2活化的调控机制尚未明确。结合miRNA表达谱筛选和ITRAq定量蛋白质组检测，我们提出心梗后ILC2内显著上调的miR-21，极有可能通过靶基因Spry1和PTEN，调控下游信号通路，从而促进ILC2活化的假说。下一步拟构建ILC2细胞内诱导性敲除miR-21的小鼠，采用流式分选和多参数分析技术，建立ILC2活化细胞与心脏成纤维细胞的共培养体系，明确ILC2在miR-21的调控下活化，对心梗后心肌纤维化的促进作用；并深入阐明miR-21通过靶向Spry1和PTEN，调控ILC2活化的分子机制。以期为临床防治心梗后心肌纤维化拓展免疫新策略和干预新靶标。

Myocardial fibrosis is the main factor contributing to myocardial remodeling and heart failure post-myocardial infarction, in which immune response plays a key role. Studies have demonstrated that type 2 innate lymphoid cells (ILC2) activation can mediate tissue fibrosis. Our previous study discovered that myocardial fibrosis was attenuated remarkably post-myocardial infarction in mice with ILC2 deficiency, indicating that ILC2 activation could mediate myocardial fibrosis. However, the regulatory mechanism of ILC2 activation in this process remains unclear. Based on the evidence of miRNA expression profile screening and ITRAq quantitative proteomics analysis, we postulate that it is most likely the significant up-regulation of miR-21 in ILC2 post-myocardial infarction that promotes ILC2 activation by regulating the downstream signaling pathway via the target genes Spry1 and PTEN. In our ongoing study, we plan to inducible conditionally knock out miR-21 in mouse ILC2, use fluorescence activated cell sorting, multi-parameter flow cytometry analysis techniques, and establish a co-culture system of activated ILC2 and cardiac fibroblasts to determine how ILC2 activation promotes myocardial fibrosis via miR-21 mediation post-myocardial infarction, and further elucidate the molecular mechanism underlying the regulatory effect of miR-21 on ILC2 activation via the target genes Spry1 and PTEN, hoping that the results could provide evidence-based clues for developing new immunological strategies and intervention targets for the clinical prevention and treatment of myocardial fibrosis post-myocardial infarction.