PI3K/AKT/mTOR 信号通路通过调控 Th17 细胞分化 参与 EAT 小鼠甲状腺自身免疫损伤.

何呈燕; 李依雯; 甘玲; 王珏; 薛海波

Objective To explore the role and mechanism of phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin kinase (PI3K/AKT/mTOR) signaling in autoimmune thyroiditis (AIT). Methods 24 female C57BL/6 mice were randomly divided into four groups：a normal control (NC) group, an experimental autoimmune thyroiditis (EAT) group, and two groups treated with LY294002 (25 mg/kg or 50 mg/kg LY294002). The degree of thyroiditis was observed by hematoxylin and eosin staining. The percentage of Th17 cells in the spleen mononuclear cells (SMCs) was determined by flow cytometry. Enzyme-linked immunosorbent assay was used to measure the concentrations of thyroglobulin antibody (TgAb) and interleukin-17A (IL-17A) in the serum. Western blotting was conducted to detect the protein levels of IL-17A, p-AKT (Thr308), p-AKT (Ser473), p-mTOR (Ser2448), S6K1, and S6K2 in the different groups. Results Compared with the NC group, the infiltration of Th17 cells and the expressions of IL-17A, p-AKT (Ser473), p-AKT (Thr308), p-mTOR (Ser2448), S6K1, and S6K2 rose remarkably in EAT mice. After the PI3K pathway was blocked, the degree of thyroiditis was significantly alleviated, followed by the proportion of Th17 cells, and the expression of IL-17A and PI3K pathway-related molecules decreased in a dose-dependent manner. Conclusion PI3K/AKT/mTOR signaling pathway participates in thyroid autoimmune jnjury of EAT mice by regulating Th17 cells differentiation.

T helper cells; HEMATOXYLIN & eosin staining; AUTOIMMUNE thyroiditis; ENZYME-linked immunosorbent assay; CELL differentiation

Journal of China Medical University, 2024, Vol 53, Issue 11, p972

0258-4646

Academic Journal