Buzhong Yiqi Decoction Regulates Th17 Cells Differentiation in Autoimmune Thyroiditis through PTEN/AKT-immunometabolism Axis

Introduction: Autoimmune thyroiditis (AIT), a prevalent autoimmune disorder, can severely impair patients' quality of life when progressing to hypothyroidism. This investigation seeks to systematically evaluate the therapeutic efficacy of Buzhong Yiqi Decoction (BZYQ) against iodine-induced AIT while elucidating its underlying molecular mechanisms. Methods: NOD.H-2^h4 mice received daily 0.05% sodium iodide gavage for 8 weeks to induce AIT. Thyroid histopathology was evaluated by HE staining. Serum autoantibody levels and lactate concentrations were measured. Western blotting analyzed PTEN, p-PI3K/PI3K, p-AKT/AKT, GLUT1, HK2, PKM2, and LDHA protein expression in thyroid tissues. Immunofluorescence staining localized the expression of HK2 and RORγt in thyroid sections. Flow cytometry quantified the proportion of Th17 cells within splenic lymphocytes. Results: BZYQ reduced thyroid structural damage and lymphocytic infiltration in AIT mice, accompanied by significant reductions in serum TGAb and TPOAb levels. Notably, BZYQ modulated glycolysis to decrease lactate levels and the proportion of Th17 cells. Mechanistically, BZYQ upregulated PTEN expression to suppress downstream p-PI3K, p-AKT, GLUT1, HK2, PKM2, and LDHA expression, thereby achieving regulation of immunometabolic pathways. Discussion: This study provides experimental evidence for broadening the modern clinical applications of this classical formula. However, the related mechanisms still require further rigorous clinical studies for validation. Conclusion: BZYQ modulates Th17 differentiation via the PTEN/AKT-immunometabolic axis in AIT. .