IDO1/Kyn/AhR信号下调作用于Tregs细胞调控桥本甲状腺炎发病的机制研究

调节性T细胞（Tregs）是机体维持自我耐受的最关键细胞，其免疫抑制作用下调是桥本甲状腺炎（HT）关键致病环节，机制不明。近年来，免疫细胞的代谢及其调节已成为免疫炎症性疾病的新研究领域。课题组前期采用液质联用技术发现HT患者和小鼠血清IDO1/Kyn/AhR信号介导的色氨酸代谢显著下调，而后者被证明是Tregs细胞增殖和活化的重要代谢开关。故此，我们推测下调的IDO1/Kyn/AhR信号通过作用于Tregs参与HT发病。本研究们拟采用人群-动物模型研究模式：人群研究分析IDO1/Kyn/AhR信号下调与HT中Tregs（数目和功能标志物）的关联，两者间的因果关系随后在动物模型上通过药物Tranilast、TCDD激活IDO1/Kyn/AhR信号不同位点进行验证。如此，有希望为HT的发病机制和免疫治疗提供新视野。

Regulatory T cells (Tregs) are critical for maintaining self-tolerance, and their weakened inhibitory effect is the key pathogenic link to Hashimoto's thyroiditis (HT), but the potential mechanisms are unclear. Recently, studies have shown that metabolic regulation of immune cells has become a new research field in immune-mediated inflammatory diseases. Our previous work based on liquid chromatograph mass spectrometer found that tryptophan metabolism mediated by IDO1-Kyn-AhR signaling, as a key metabolic switch for Tregs proliferation and activation, were significantly down-regulated in serum of patients and mice with HT. In view of these, it is reasonably speculated that down-regulation of IDO1-Kyn-AhR signaling may contribute to HT via Tregs. Therefore, this project aims to integrate human and animal research. Population research focus on analyzing the relationship between the IDO1-Kyn-AhR signaling and Tregs (numbers and function markers) in HT. The causal relationship between them was further verified in animal models by activating different sites of IDO1-Kyn-AhR signaling with drugs Tranilast or TCDD, hoping for providing a new perspective for the pathogenesis and immunotherapy of HT.