Disruption of thyroid-intrinsic clock aggravates experimental autoimmune thyroiditis.

Area of Science:

• Immunology
• Chronobiology
• Endocrinology

Background:

• The core clock gene Bmal1 is linked to inflammatory and autoimmune diseases.
• Previous research showed light shifts disrupt the thyroid clock and worsen autoimmune thyroiditis (AIT).

Purpose of the Study:

• To investigate the specific role of the thyroid clock in autoimmune thyroiditis (AIT).
• To examine the impact of Bmal1 in thyrocytes on AIT development and severity.

Main Methods:

• Utilized a thyrocyte-specific Bmal1 knockdown (cKO) mouse model.
• Compared experimental autoimmune thyroiditis (EAT) severity in cKO and control mice under different immunization time points.
• Measured anti-thyroglobulin antibodies (TgAb), inflammatory cytokines, and CD4+ T cell responses.

Main Results:

• Bmal1 knockdown in thyrocytes disrupted intrathyroidal clock gene rhythmicity.
• Both cKO and control mice showed more severe EAT when immunized at ZT6 versus ZT18.
• cKO-EAT mice exhibited higher TgAb levels, increased inflammatory cytokines, and enhanced CD4+ T cell responses compared to controls.

Conclusions:

• Bmal1 plays a novel role in regulating the thyroid clock.
• Thyroid Bmal1 modulates the severity of experimental autoimmune thyroiditis (EAT).
• Circadian regulation is a previously unrecognized factor in thyroid autoimmune disease.