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缺氧环境下调节性T细胞对血管内皮细胞的调控作用

The Regulatory Role of Regulatory T Cells on Vascular Endothelial Cells in Hypoxic Environments

  • 摘要: 组织修复的本质是多系统高度协调的生物学过程,血管网络的有序重建是关键环节之一。既往研究聚焦天然免疫细胞对血管内皮细胞的调控作用近年来,研究者发现,适应性免疫细胞在组织修复中发挥着重要作用。然而,关于适应性免疫细胞与血管内皮细胞间相互作用的研究较少,其中,调节性T细胞在维持免疫稳态和塑造组织修复微环境中发挥着关键作用,深入探索其对血管内皮细胞的调控作用有助于阐明组织修复过程中适应性免疫系统如何调控血管重建过程。本研究通过建立缺氧细胞培养体系模拟损伤后缺氧微环境,发现缺氧环境上调了Jurkat T细胞中HIF-1α的表达,并促进了Jurkat T细胞的FOXP3表达,呈现调节性T细胞表型。与血管内皮细胞的共培养结果表明,调节性T细能够显著增强血管内皮细胞的迁移与成血管能力。RNA-seq转录组测序揭示,缺氧原代调节性T细胞通过激活血管内皮生长因子等信号通路重塑血管内皮细胞功能。本研究结果表明,调节性T细胞在缺氧环境中能够促进血管内皮细胞重建血管网络,为免疫-血管协同治疗提供了新靶点。

     

    Abstract: Tissue repair is essentially a highly coordinated biological process involving multiple systems, and the orderly reconstruction of the vascular network is one of its key components. Previous studies have focused on the regulation of vascular endothelial cells by innate immune cells. In recent years, researchers have discovered that adaptive immune cells play a significant role in tissue repair. However, studies on the interactions between adaptive immune cells and vascular endothelial cells remain limited. Among these, regulatory T cells (Tregs) play a critical role in maintaining immune homeostasis and shaping the tissue repair microenvironment. A deeper understanding of their regulatory effects on vascular endothelial cells will help elucidate how the adaptive immune system regulates vascular reconstruction during tissue repair. In this study, we established a hypoxic cell culture model to simulate the hypoxic microenvironment following injury. We found that the hypoxic environment upregulated HIF-1α expression in Jurkat T cells and promoted FOXP3 expression, resulting in a Treg phenotype. Results from co-culture experiments with vascular endothelial cells indicate that regulatory T cells can significantly enhance the migration and angiogenesis capabilities of vascular endothelial cells. RNA-seq transcriptomic analysis revealed that hypoxic primary Treg cells remodel vascular endothelial cell function by activating signaling pathways such as VEGF. This study demonstrates that Treg cells can promote the reconstruction of vascular networks by vascular endothelial cells in a hypoxic environment, providing new therapeutic targets for immune-vascular synergistic therapy.

     

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