Disruption of thyroid-intrinsic clock aggravates experimental autoimmune thyroiditis

The core clock gene Bmal1 has been associated with the development of a variety of inflammatory diseases, with its deletion shown to induce or aggravate autoimmune disease in a tissue-specific pattern. Building on our previous findings that light shift can disrupt thyroid clock and exacerbate autoimmune thyroiditis (AIT), we investigated the specific role of the thyroid clock in AIT using a thyrocyte-specific Bmal1 knockdown mouse model (cKO). Our study revealed that Bmal1 knockdown in thyrocytes disrupted the rhythmic expression of intrathyroidal clock genes. Both cKO and Ctrl mice exhibited more severe experimental autoimmune thyroiditis (EAT) when immunized at ZT6 compared to ZT18. However, cKO-EAT mice showed elevated levels of anti-thyroglobulin antibodies (TgAb) and inflammatory cytokines compared to Ctrl-EAT mice, which correlated with CD4+ T cell-mediated immune responses. These findings highlight a novel role for Bmal1 in regulating the thyroid clock and modulating the severity of EAT, uncovering a previously unrecognized connection between circadian regulation and thyroid autoimmune disease.