AdipoR1 通过调节 HIF-1α 依赖性糖酵解在调控 Th17 细胞分化中的关键作用。
Critical Role of AdipoR1 in Regulating Th17 Cell Differentiation Through Modulation of HIF-1α-Dependent Glycolysis.
机构信息
Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
出版信息
Front Immunol. 2020 Aug 18;11:2040. doi: 10.3389/fimmu.2020.02040. eCollection 2020.
We previously reported that adiponectin (AD) promotes naïve T cell differentiation into Th17 cells and participates in synovial inflammation and the bone erosion process in patients with rheumatoid arthritis. Here, we use a T cell lineage adiponectin receptor 1 (AdipoR1) conditional knockout model to investigate the role of AdipoR1 in Th17 differentiation. RNA-sequencing (RNA-seq) demonstrated that knockout reduced the expression of a variety of T cell related genes, with showing the greatest level of down-regulation. AdipoR1 deficiency inhibited Th17 cell differentiation and ameliorated joint inflammation in antigen-induced arthritis mice. Moreover, AdipoR1-deficent CD4T cells displayed reduced Hypoxia-Inducible Factor-1α expression leading to glycolysis inhibition during naïve CD4T cell differentiation into Th17 cells. We describe a novel function of AdipoR1 in regulating Th17 cell differentiation through modulating HIF-1α-dependent glycolysis.
我们之前曾报道过脂联素（AD）可促进初始 T 细胞分化为 Th17 细胞，并参与类风湿关节炎患者的滑膜炎症和骨侵蚀过程。在这里，我们使用 T 细胞谱系脂联素受体 1（AdipoR1）条件性敲除模型来研究 AdipoR1 在 Th17 分化中的作用。RNA 测序（RNA-seq）表明，AdipoR1 缺失减少了多种 T 细胞相关基因的表达，其中下调最为显著。AdipoR1 缺失抑制了 Th17 细胞分化，并改善了抗原诱导关节炎小鼠的关节炎症。此外，AdipoR1 缺陷型 CD4T 细胞显示出低水平的缺氧诱导因子-1α（Hypoxia-Inducible Factor-1α，HIF-1α）表达，导致在初始 CD4T 细胞分化为 Th17 细胞过程中糖酵解受到抑制。我们描述了 AdipoR1 通过调节 HIF-1α 依赖性糖酵解来调节 Th17 细胞分化的新功能。
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