Pharmacological suppression of NLRP3 inflammasome attenuated the development of autoimmune thyroiditis.

Autoimmune thyroiditis (AIT), characterized by an endless inflammatory process of self-destruction, ultimately leads to chronic swelling of the thyroid gland and its dysfunction. Here, we investigated the involvement of the NLR pyrin domain-containing 3 (NLRP3) inflammasome in AIT development. We found that NLRP3 is significantly upregulated in the thyroid of AIT patients and mice with experimental autoimmune thyroiditis (EAT). Pharmacological suppression of NLRP3 using its inhibitor MCC950 suppressed the progression of EAT in vivo. Furthermore, MCC950 treatment significantly reduced the numbers of infiltrating CD4+ and CD8+ T cells in the thyroid. Moreover, MCC950 significantly lowered the amounts of T helper 1 cells, T helper 17 cells, interferon gamma, and interleukin-17A; however, it significantly increased regulatory-T-cell numbers and interleukin-10 levels. These results suggest that suppression of NLRP3 inflammasome activation reverses AIT by inhibiting Th1- and Th17-cell responses and promoting Treg cell responses. Hence, the NLRP3 inflammasome is a promising therapeutic and theragnostic target in AIT. inhibits Th1- and Th17-cell responses and promotes Treg cell responses.