2型固有淋巴细胞在AMI后心室重塑中的作用和机制研究

Recent studies show that ventricular remodeling after acute myocardial infarction (AMI) is closely related to immune inflammation. Type 2 innate lymphoid cells (ILC2s) belong to the innate immune system and play an important role in a variety of inflammation-related diseases by generating effector molecules such as IL-13/IL-5/Areg. Our previous study found increased ILC2s in the heart after AMI. Besides，adoptive transfer of ILC2s significantly reduced ventricular remodeling and improved cardiac function after AMI. Therefore, we believe that ILC2s play a protective role in ventricular remodeling after AMI, and its specific mechanism needs to be further elucidated. This project intends to: ① observe the expression of ILC2s after AMI; ② observe the effects of ILC2s replenishment or deleption on ventricular remodeling after AMI through adoptive transfer ILC2s or ILC2KO mice; ③ observed deleption or replenishment ILC2s from the source of different mice (WT/IL-13KO/IL-5KO/AregKO) on monocytes and macrophages after AMI, to investigate the target cells and functional mediators of ILC2s. These exploratory studies will lead to a comprehensive understanding of the role of ILC2s in ventricular remodeling after AMI, and provide the theoretical and experimental basis for the development of targeted therapy in ventricular remodeling after AMI.

研究表明急性心肌梗死（AMI）后心室重塑与炎症关系密切。2型固有淋巴细胞（ILC2s）属于固有免疫系统，通过产生IL-13/IL-5/Areg等效应分子在多种炎症相关疾病中发挥重要作用。我们的前期研究发现AMI后心脏中ILC2s增多，过继转输ILC2s明显减轻AMI后的心室重塑并改善心功能。因此我们认为ILC2s在AMI后心室重塑中具有保护作用，其具体机制有待进一步阐明。本项目拟：①观察AMI后ILC2s的表达规律；②应用ILC2s过继转输或ILC2KO小鼠观察增加或去除IL2Cs对AMI后心室重塑的影响；③观察去除或增加不同小鼠来源（WT/IL-13KO/IL-5KO/AregKO）的ILC2s对AMI后单核细胞，巨噬细胞的影响，明确ILC2s调控AMI后心室重塑的靶细胞和效应分子。最终深入地阐明ILC2s在AMI后心室重塑中的保护作用和机制，为AMI后心室重塑的靶向治疗提供理论基础。

近年来的研究表明急性心肌梗死（AMI）后的心室重塑与免疫炎症关系密切。2型固有淋巴样细胞（ILC2s）属于固有免疫系统，通过产生IL-13、IL -9、IL-4等效应分子在多种炎症相关疾病中发挥重要作用。我们研究发现ILC2s细胞在AMI后小鼠心脏局部表达增高，并于急性心肌梗死后7天到达高峰。过继转输ILC2s细胞可改善AMI后心脏功能及减小梗死面积，而IL2CKO小鼠AMI后心功能恶化、梗死面积增加，提示ILC2s细胞在AMI后发挥保护作用。我们进一步的机制研究表明，IL2Cs细胞不影响AMI后中性粒细胞、T细胞及其亚群的浸润，但减少AMI后心肌局部单核细胞的浸润并促进巨噬细胞向M2型极化。此外，通过过继转输不同敲基因小鼠来源的ILC2s细胞，我们证实了IL-13是其重要的效应分子。我们的研究完善了AMI的免疫炎症理论，有望为AMI炎症的靶向治疗提供新的理论基础和实验依据。