Department of Molecular Medicine, Atomic Bomb Disease Institute, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
J Endocrinol. 2011 Jun;209(3):353-7. doi: 10.1530/JOE-11-0129. Epub 2011 Apr 7.
Experimental Graves'-like hyperthyroidism can be induced in susceptible mouse strains by repetitive immunizations with recombinant adenovirus expressing the human full-length TSH receptor (TSHR) or its A-subunit. Previous studies have shown that splenocytes from immunized mice produce interferon (IFN)-γ and interleukin (IL) 10 in response to antigen stimulation in an in vitro T cell recall assay. Although IFN-γ is now well known to be essential for disease induction, the role(s) played by IL10 are unknown. Therefore, this study was conducted to clarify the significance of endogenous IL10 in the pathogenesis of experimental Graves' disease using IL10 deficient (IL10(-/-)) mice. Our results show that T cell response was augmented when estimated by their antigen-specific secretion of the key cytokine IFN-γ, but B cell function was dampened, that is, anti-TSHR antibody titers were decreased in IL10(-/-) mice, resulting in a lower incidence of Graves' hyperthyroidism (54% in IL10(+/+) vs 25% in IL10(-/-)). Thus, in addition to IFN-γ, these data clarified the role of IL10 for optimizing anti-TSHR antibody induction and eliciting Graves' hyperthyroidism in our Graves' mouse model.
实验性格雷夫斯样甲状腺功能亢进症可通过重复免疫重组腺病毒表达人类全长 TSH 受体（TSHR）或其 A 亚单位在易感小鼠品系中诱导。先前的研究表明，来自免疫小鼠的脾细胞在体外 T 细胞回忆测定中对抗原刺激产生干扰素（IFN）-γ和白细胞介素（IL）10。虽然现在众所周知 IFN-γ对于疾病诱导是必不可少的，但 IL10 的作用尚不清楚。因此，这项研究旨在使用 IL10 缺陷（IL10（-/-））小鼠阐明内源性 IL10 在实验性格雷夫斯病发病机制中的意义。我们的结果表明，当通过其关键细胞因子 IFN-γ的抗原特异性分泌来估计 T 细胞反应时，T 细胞反应增强，但 B 细胞功能受到抑制，即抗 TSHR 抗体滴度在 IL10（-/-）小鼠中降低，导致格雷夫斯甲状腺功能亢进（IL10（+/+）中的 54%与 IL10（-/-）中的 25%）的发生率较低。因此，除了 IFN-γ 外，这些数据还阐明了 IL10 在我们的格雷夫斯氏病小鼠模型中优化抗 TSHR 抗体诱导和引发格雷夫斯氏甲状腺功能亢进症的作用。
