DCs源外泌体中miR-493-5p靶向FOXO1调控Th9细胞分化促进哮喘发生的机制研究

Th9细胞及其分泌的IL-9在哮喘免疫病理中起着重要的作用，有报道证实FOXO1是CD4+T细胞向Th9细胞方向分化的过程中关键转录因子，但是具体的调控机制尚不清楚。研究发现，微小RNA（miRNA）可通过调控FOXO1进而影响Th细胞分化。基于此，前期我们从哮喘患儿外周血单个核细胞中筛选并证实参与调控Th9细胞分化且靶向FOXO1的miR-493-5p，并进一步明确了miR-493-5p的来源于树突状细胞（DCs），而DCs亦是参与哮喘发病过程的重要细胞。鉴此，本项目拟以Th9细胞分化调控为切入点，进一步探讨DCs来源外泌体中miR-493-5p介导FOXO1调控Th9细胞分化的作用及机制，明确DCs源Exosome中miR-493-5p在哮喘模型中的干预效果。本项目所获研究结果为更全面认识Th9/IL-9在哮喘免疫病理中的作用提供新线索，为哮喘的防治提供新的理论依据和潜在的干预靶标。

The Th9 cells and cytokine IL-9 play an important role in the immunopathology of asthma. It has been reported that FOXO1 is a key transcription factor in the differentiation of CD4+T cells into Th9 cells, but the specific regulatory mechanism is still unclear. It has been found that microRNA (miRNA) can affect the differentiation of Th cells by regulating FOXO1. Based on this, we previously screened and confirmed miR-493-5p from peripheral blood mononuclear cells of asthmatic children, which is involved in regulating Th9 cell differentiation and targeting FOXO1, and further confirmed that miR-493-5p is in exosomes derived from dendritic cells (DCs), and DCs are also important cells involved in the pathogenesis of asthma. In view of this, this project intends to further explore the role and mechanism of miR-493-5p in exosomes derived from DCs mediated FOXO1 regulation of Th9 cell differentiation, and clarify the intervention effect of miR-493-5p in exosomes derived from DCs in asthma model. The results of this project provide new clues for a more comprehensive understanding of the role of Th9 (IL-9) in asthma immunopathology, and provide new theoretical basis and potential intervention targets for the prevention and treatment of asthma.