Autoimmune thyroiditis (AIT) is a well-known organ-specific autoimmune disease. Hashimoto’s thyroiditis is a prevalent subtype of AIT that has been diagnosed by means of both hypothyroidism and thyrotoxicosis, which are induced by thyroid autoantibody production [viz. thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb)] and by lymphocytic infiltration of the thyroid] [1]. According to experimental studies involving animal models with genetic susceptibility as well as epidemiological studies, the number of severe AIT cases with high iodine consumption has risen significantly [2], [3]. Nonetheless, to date, the exact mechanisms of AIT remain unknown. Elucidating AIT pathogenesis will undoubtedly facilitate AIT diagnosis and prevention.

The NLR pyrin domain-containing 3 (NLRP3) inflammasome is an indispensable component of innate immunity. It primarily comprises a sensor (NLRP3), an adaptor protein [apoptosis-associated speck-like protein carrying a C-terminal caspase recruitment domain (CARD)], and an effector (caspase 1). Aside from NLRP3 inflammasome assembly, caspase 1 may be activated through self-cleavage and then proteolytically processes pro-interleukin (IL)-1β and pro-IL-18, thereby creating active IL-1β and IL-18 and provoking pyro ptosis, a type of inflammatory programmed cell death [4]. Initial research revealed that NLRP3 inflammasome activation partakes in a fundamental molecular pathway underlying ischemic stroke in diabetic mice and retinal ischemic/reperfusion injuries [5], [6]. Several researchers have later demonstrated that the NLRP3 inflammasome takes part in acute skin allograft rejection and is crucial for the control of obliterative bronchiolitis after a lung transplant [7], [8]. Despite NLRP3’s practical importance, its possible usefulness for AIT management is still poorly investigated.

The present work revealed 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 repressed both T helper 1 (Th1) and Th17 responses and promoted regulatory T cell (Treg) responses, thereby attenuating EAT progression in vivo. Therefore, suppression of NLRP3 may be an innovative preventive strategy against AIT-associated inflammatory processes.