自身免疫甲状腺炎（AIT）是器官特异性自身免疫病，发病机制仍未明。碘致甲状腺细胞损伤，树突状细胞（DCs）以及甲状腺细胞本身呈递自身抗原打破免疫耐受，自身反应性T细胞分化失衡是AIT重要的免疫学发病机制。外泌体是直径30-100 nm间的微泡，由不同类型细胞分泌，其内囊括蛋白质、核酸、脂类等成分，在抗原呈递、免疫激活、肿瘤转移等方面发挥重要作用。损伤细胞来源的外泌体中含有Toll样受体(TLRs)的配体，激活NF-κB通路促进DCs成熟，诱导CD4+T细胞分化失衡。1型糖尿病、类风湿性关节炎等多种自身免疫病中均发现受累靶细胞来源的外泌体呈递自身抗原，激活DCs，诱导T细胞分化。本课题将探究受损甲状腺细胞来源的外泌体在自身抗原提呈、DCs激活、T细胞分化失衡等环节的作用及其参与AIT发生发展的具体机制；阻断DC细胞TLR通路或抑制甲状腺细胞外泌体分泌可能为寻找新的AIT治疗策略提供理论依据。

Autoimmune thyroiditis (AIT) is a common organ-specific autoimmune disease,of which the pathogenesis is not well verified yet. It has been reported that the damages to thyrocytes induced by high iodine, the presentation of autoantigens by dendritic cells (DCs) and thyrocyte itself can lead to break down of immune tolerance, and the imbalanced differentiations of auto-reactive T lymphocytes are also involved in the development of AIT. Exosomes, with the diameter of 30-100nm, containing proteins,lipids and nucleic acids, derive from diverse types of cells and play important roles in antigen presentation, immunity activation and tumor metastasis. It has been found in some autoimmune diseases including type 1 diabetes and rheumatoid arthritis that damaged target cells-derived exosomes carrying with the ligands of TLRs can promote DCs maturation via the NF-kappa B pathway and consequently disturb the balenced differentiation of the CD4+T cells. This study aims at exploring the roles and mechanisms of exosomes derived from damaged thyrocytes of AIT in the aspects of antigen presentation, DCs activation and T lymphocytes differentiation and trying to provide theoretical basis for finding novel therapeutic strategies of AIT through blocking TLR signaling in DCs or inhibiting the exosomes secretion of thyrocytes.