Influence of signal transducer and activator of transcription-1 signaling on thyroid morphology and function

Interferon (IFN)-gamma 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 IFN gamma on thyroid morphology and function, we crossed transgenic mice that express IFN gamma specifically in the thyroid gland to mice deficient in STAT1. Lack of STAT1 ameliorated the abnormal thyroid morphology and the primary hypothyroidism typical of IFN gamma transgenic mice but not the suppressed iodine accumulation. Interestingly, lack of STAT1 alone decreased iodine accumulation, seemingly through expression of TGFbeta. These results indicate that STAT1 is required to mediate some but not all of the phenotypic changes induced by IFN gamma and that it also regulates iodine accumulation via TGFbeta signaling.