Interferon (IFN)-γ has been involved in the pathogenesis of Hashimoto thyroiditis. It is a cytokine released by infiltrating mononuclear cells that mediates its actions mainly through signal transducer and activator of transcription-1 (STAT1) but also through other transcription factors. To dissect the effect of IFNγ on thyroid morphology and function, we crossed transgenic mice that express IFNγ specifically in the thyroid gland to mice deficient in STAT1. Lack of STAT1 ameliorated the abnormal thyroid morphology and the primary hypothyroidism typical of IFNγ transgenic mice but not the suppressed iodine accumulation. Interestingly, lack of STAT1 alone decreased iodine accumulation, seemingly through expression of TGFβ. These results indicate that STAT1 is required to mediate some but not all of the phenotypic changes induced by IFNγ and that it also regulates iodine accumulation via TGFβ signaling.
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