Study Title:

Vitamin D and Hyperthyroid

Study Abstract

Thyrotropin receptor (TSHR) antibodies and hyperthyroidism are induced by immunizing mice with adenovirus encoding the TSHR or it's A-subunit. Depleting regulatory T cells (Treg) exacerbates thyrotoxicosis in susceptible BALB/c, and induces hyperthyroidism in normally resistant C57BL/6, mice. Vitamin D plays an important role in immunity: high dietary vitamin D intake suppresses (and low intake enhances) adaptive immune responses. Vitamin D induced immunosuppression may enhance Treg. Therefore, we hypothesized that decreased vitamin D intake would mimic Treg depletion and enhance hyperthyroidism induced by A-subunit adenovirus immunization. BALB/c mice had a reduced ability versus C57BL/6 mice to generate the active metabolite of vitamin D [1,25(OD)2D3 ]. Vitamin D deficiency induced subtle immune changes in BALB/c (not C57BL/6) mice. Compared with mice fed regular chow, vitamin D deprived BALB/c had fewer splenic B cells, decreased IFN- responses to mitogen, and lacked memory T cell responses to A-subunit protein. However, vitamin D deficiency did not alter TSHR antibody responses measured by ELISA, TSH binding inhibition or cAMP generation from TSHR-expressing cells. Unexpectedly, compared with vitamin D-sufficient mice, vitamin D-deficient BALB/c mice had lower pre-immunization thyroxine levels and developed persistent hyperthyroidism. This difference was unrelated to the immunological changes between vitamin D deficient - or sufficient- animals. Previously, we found that different chromosomes or loci confer susceptibility to TSHR antibody induction versus thyroid function. Our present studies provide evidence that an environmental factor, vitamin D, has only minor effects on induced immunity to the TSHR, but directly affects thyroid function in mice.

From press release:
Vitamin D may directly affect thyroid function, according to research in a preclinical animal model published online Oct. 16 in Endocrinology.

Alexander Misharin of the UCLA School of Medicine in Los Angeles and colleagues tested the role of vitamin D in a mouse model of Graves' disease, in which hyperthyroidism is induced by immunization with an adenovirus encoding the thyrotropin receptor. Because it was previously established that vitamin D enhances regulatory T cells, the authors hypothesized that decreasing vitamin D through a controlled diet would intensify the severity of Graves' disease in the model.

Vitamin D deficiency induced only small immunological changes. Unexpectedly, the vitamin D-deprived mice developed persistent hyperthyroidism following immunization, unlike their vitamin D-sufficient matched controls. This disparity was not explained by any immunological difference, and the authors speculated that the persistent hyperthyroidism was instead caused by an increased sensitivity of the thyroid to the antibodies directed against thyrotropin.

"Rather than affecting the immune response, the most important effect of vitamin D deficiency was on the thyroid," the authors write, providing evidence for the role of an environmental factor, vitamin D, on thyroid function.

Study Information

Alexander Misharin, Martin Hewison, Chun-Rong Chen, Venu Lagishetty, Holly A. Aliesky, Yumiko Mizutori, Basil Rapoport, and Sandra M. McLachlan.
Vitamin D deficiency modulates Graves' hyperthyroidism induced in BALB/c mice by thyrotropin receptor immunization.
2008 October
Autoimmune Disease Unit, Cedars-Sinai Research Institute and UCLA School of Medicine, 8700 Beverly Blvd, Suite B-131, Los Angeles, CA.

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