circRNA102179-miR155的CeRNA网络调控Treg/Th17细胞分化失衡的作用与机制研究

The imbalance of Treg/Th17 differentiation is an important mechanism of immunologic derangement and severe dysregulated inflammatory reactions in Sepsis. Based on the pilot clinical trial by microarray analysis and bioinformatic analysis, CeRNA network dominated circRNA102719 co-binding site miR-155 with PTPN2 mRNA promote CD4+ T cells to Treg and inhibit differentiation from CD4+ T cells to Th17, promoting T cell-mediated host immunopathology and excessive inflammation in Sepsis. Therefore, it is hypothesized that the circRNA102719 is down-regulated in patients with Sepsis, releasing miR-155 bound by circRNA102719, which targets to inhibit PTPN2 and reduce Treg/Th17, mediating immune derangement and severe inflammatory reactions. By various methods, we will investigate the relationship between circRNA102719 and the imbalance differentiation of Treg/Th17, and their regulatory mechanism in Sepsis at various levels, including molecular, cellular, animal and clinical study, exploring the interaction between circRNA102719, miR-155, and PTPN2mRNA. Our work explores the mechanisms of circRNA102719 on immune system dysfunction and inflammatory injury in patients with Sepsis and provides a great potential target as a biomarker in diagnosis and a new strategy for the treatment of Sepsis.

Treg/Th17失衡是脓毒症免疫损伤的重要机制。在前期Sepsis 患者临床筛查基因芯片预试验基础上，结合生物信息数据库预测发现由circRNA102719主导CeRNA网络的调控靶点miR-155介导Sepsis中Treg/Th17分化失衡，circRNA102719通过与PTPN2mRNA共同结合位点miR-155，促进CD4+ T细胞向Treg、抑制其向Th17分化，加重炎症损伤。据此假设：脓毒症患者circRNA102719下调，释放被其结合的miR-155，靶向抑制PTPN2使Treg/Th17降低，介导炎症损伤。本研究分别在分子、细胞、动物和临床多层次探究circRNA与Treg/Th17分化失衡的关系及在脓毒症中的调控机制，证实circRNA102719、miR-155、PTPN2之间的互作关系，深入解析circRNA102719对脓毒症免疫损伤的调控机制，为精准调控Sepsis免疫损伤提供基础。

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