自身免疫甲状腺炎（AIT）是患病率高、危害面广的内分泌疾病。其致病性免疫应答异常的具体机制尚未明晰。TAM受体（TYRO3、AXL和MERTK）及其配体（GAS6和PROS1）介导的信号通路是维持免疫稳态的重要环节。已有线索提示该通路可能成为AIT机制研究的新切入点。本课题围绕两个科学假设开展：AIT中TAM受体及其配体的表达改变；AIT中TAM受体信号通路未能正常发挥对免疫炎症反应的负调控功能，造成TLRs通路相对激活和凋亡细胞清除不利。研究将首先揭示TAM受体及其配体在AIT患者和动物模型中的表达和定位；利用动物模型和体外实验探讨在AIT发生发展中，TAM受体信号通路介导的免疫稳态调控有无缺陷，外源性给予配体激活TAM通路有无治疗作用；通过体外实验探讨TAM受体信号通路在AIT中与激动免疫炎症的TLRs通路的相互作用。课题将丰富我们的AIT机制研究系列，为AIT的防治寻找新靶点和策略。

Autoimmune thyroiditis (AIT) represents a high prevalence and a variety of adverse effects on health. Its immunologic pathogenesis remains unclear. The TAM receptor tyrosine kinases (RTKs)—TYRO3, AXL, and MERTK—together with their cognate agonists GAS6 and PROS1 function to restore homeostasis. There are hints that TAM receptor signaling may play an important role in AIT. Therefore, we hypothesized that expressions of TAM RTKs and their agonists exist alteration in AIT, and that negative regulations of TAM signaling in the resolution of immune response are impaired in AIT, which may contribute to uncontrolled activation of Toll-like receptor (TLR) signaling and decreased phagocytic removal of apoptotic cells. The present project aims to: 1) Demonstrate the expression and localization of TAM RTKs and their agonists in AIT patients and mouse models. 2) Explore potential deficiencies functions of TAM signaling in AIT and therapeutic value of exogenous administration of TAM agonists both in vivo and in vitro. 3) Investigate interactions between TAM signaling and TLR signaling in AIT in vitro. Results of the project are supposed to enrich our understanding in mechanisms of development of AIT, and deliver a novel and promising data for potential application.