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Disruption of thyroid-intrinsic clock aggravates experimental autoimmune thyroiditis.

Jinrong Fu, Rili Gao, Qiting Ye

    Journal of Molecular Endocrinology
    |February 25, 2025
    PubMed
    Summary
    This summary is machine-generated.

    The core clock gene Bmal1 regulates the thyroid clock and influences autoimmune thyroiditis severity. Knocking down Bmal1 in thyroid cells worsens autoimmune thyroiditis by increasing antibodies and inflammation.

    Keywords:
    Bmal1autoimmuneclock genethyroidthyroiditis

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    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.