Circadian clock disruption in autoimmune thyroiditis

Abstract

Objective: A vicious cycle between circadian disruption and escalating immune responses has been described in diverse inflammatory disease. The current study aimed to explore the role of circadian clock disruption in autoimmune thyroiditi s (AIT). Methods: Thirty AIT patients and 30 controls were enrolled and biopsied for thyroid tissues. Alterations of core clock genes expression in AIT thyr oid tissues, and its association with serum and tissue inflammatory biomarkers were a ssessed. For animal studies, C57BL/6J mice administered with porcine thyroglobulin or PBS (as control) combined with adjuvants were sacrificed at four time points to i nvestigate the circadian characteristic of experimental autoimmune thyroiditis (EAT). Light shift (LS) conditions were used to explore the influence of external circadian disturb ance on EAT. Results: The expression of clock genes BMAL1 and PER2 was significantly reduced in thyroid tissues from AIT patients and was negatively correlated to levels of thyroid peroxidase antibodies. In mouse models, diurnal fluctuations of proinflammatory cytokines were demonstrated, and further exposing mice to LS le d to overproduction of TNF-α, IFN-γ, and anti-thyroglobulin antibodies. Circadian analysis revealed significant oscillations of Bmal1, Clock, Per2, Cry1, Ror, and Rev-erb, which was broadly disturbed in EAT, LS, and EAT + LS groups. Conclusions: This study demonstrates that expression pattern of clock genes was disrupted in AIT thyroid, and chronic circadian disruption may aggravate the inflammatory responses in AIT. Whether maintaining a regular cir cadian rhythm can alleviate autoimmune thyroid diseases warrants further research.

Keywords

• autoimmune thyroiditis
• inflammation
• clock genes
• clock disruption