Mesenchymal stem cells alleviate autoimmune thyroiditis by modulating macrophage phenotypes and through influencing the STING pathway

Background: Hashimoto's thyroiditis is a chronic autoimmune inflammatory disease with a high prevalence and currently lacks effective treatment options. Previous preclinical and clinical trials have established mesenchymal stem cells (MSCs) as a promising therapeutic approach; however, there is limited research on MSC treatment for Hashimoto's thyroiditis, and the underlying molecular mechanisms remain unclear.

Methods: MSCs isolated from 4 to 6-week-old Lewis rats were employed for thyroiditis treatment. The efficacy of MSCs was assessed through histological and serological parameters. Molecular mechanisms of MSC therapy for Hashimoto's thyroiditis were explored by examining macrophage presence within thyroid tissue and relevant pathways.

Results: In this study, we observed elevated oxidative stress and endoplasmic reticulum stress within the thyroid tissue of Hashimoto's thyroiditis patients, and MSC therapy effectively mitigated this process. Furthermore, we found that the therapeutic potential of MSCs in the EAT model depended on the STING pathway. MSCs reduced endoplasmic reticulum stress and inflammasome levels within the thyroid tissue by modulating the STING pathway. Additionally, MSCs inhibited the expression of IRE1α in thyroid tissue macrophages, thereby reducing the polarization of M1-type macrophages CONCLUSIONS: The STING pathway appears to be a crucial mechanism by which MSCs modulate macrophage polarization in thyroid tissue, offering a potential treatment for thyroiditis.

Endoplasmic reticulum stress; Hashimoto's thyroiditis; Macrophage; Mesenchymal stem cells; STING.