Trichinella spiralis excretory-secretory protein alleviates autoimmune thyroiditis by modulating Th17/Treg balance via the STAT3/STAT5 pathway.

Hashimoto's thyroiditis (HT) is an organ-specific autoimmune disease mediated by T cells. Patients with HT are generally treated with lifelong thyroid hormone therapy. Trichinella spiralis is recognized as a "master" of immunomodulation, but the immunomodulatory effect of its excretory-secretory (ES) proteins on HT remains unclear. This study established an experimental autoimmune thyroiditis (EAT) mouse model to analyze the effects of T. spiralis muscle larvae (ML) ES protein intervention on thyroid pathological changes, immune cell balance and cytokine levels. The results demonstrated that ML ES protein significantly alleviated thyroid follicular destruction and inflammatory cell infiltration in EAT mice, reducing thyroid hormone and thyroid autoantibody levels. Flow cytometry analysis revealed that ES protein intervention decreased the proportion of Th17 cells, and increased the proportion of Treg cells in EAT mice. The qPCR results indicated that ES protein down-regulated mRNA expression of IL-17A and RORγt while up-regulating IL-10 and Foxp3 in EAT mouse spleen and thyroid tissues. Serum ELISA detection showed a decrease in IL-17A, CCR6 and CCL20, and an increase in IL-10 in mice. In addition, ES protein significantly inhibited the expression of NLRP3 protein in thyroid tissue, modulated the STAT3/STAT5 signaling pathway, decreased STAT3 phosphorylation and increased STAT5 phosphorylation. rIL-17A administration reversed ES protein protective effects, exacerbating thyroid damage. In conclusion, T. spiralis ML ES protein regulates the Th17/Treg cell balance through the STAT3/STAT5 signaling pathway, inhibits the excessive IL-17A secretion and NLRP3 inflammasome activation, and mitigates thyroid inflammation in EAT mice. This research revealed that T. spiralis ML ES protein could be a potential candidate immunomodulation molecule and provides new experimental evidence for the treatment of HT.