Nagayama Yuji
Department of Medical Gene Technology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Thyroid. 2007 Oct;17(10):981-8. doi: 10.1089/thy.2007.0161.
Fifty years after the discovery of thyroid autoimmunity, several animal models of Graves' hyperthyroidism are now available. All are inducible types, and diseases are elicited by injecting living cells (professional or nonprofessional antigen-presenting cells) expressing the recombinant thyrotropin receptor (TSHR) or by DNA vaccination with TSHR cDNA in plasmid or adenovirus vectors. Thus most Graves' models are attributed to the cloning of the TSHR cDNA and involve in vivo expression of the TSHR. These breakthroughs have provided us important insights into our understanding of the pathogenesis of Graves' disease, and also indispensable means to exploring the possibility of development of novel therapeutic modalities. In particular, recent studies have begun to scrutinize the genetic factors contributing to the susceptibility to this ailment, and to delineate the roles for central and peripheral tolerance and also for fine balance between autoreactive effector T cells and regulatory T cells in the pathophysiology of anti-TSHR autoimmunity and Graves' hyperthyroidism. Moreover, preliminary, but novel, therapeutic approaches have also been started to treat experimental hyperthyroidism.
在发现甲状腺自身免疫50年后，现在已有几种格雷夫斯氏甲状腺功能亢进症的动物模型。所有这些都是诱导型模型，通过注射表达重组促甲状腺激素受体（TSHR）的活细胞（专业或非专业抗原呈递细胞）或用质粒或腺病毒载体中的TSHR cDNA进行DNA疫苗接种来引发疾病。因此，大多数格雷夫斯氏模型都归因于TSHR cDNA的克隆，并涉及TSHR的体内表达。这些突破为我们理解格雷夫斯氏病的发病机制提供了重要见解，也是探索新型治疗方法开发可能性的不可或缺的手段。特别是，最近的研究开始仔细研究导致易患这种疾病的遗传因素，并阐明中枢和外周耐受性以及自身反应性效应T细胞与调节性T细胞之间的精细平衡在抗TSHR自身免疫和格雷夫斯氏甲状腺功能亢进症病理生理学中的作用。此外，也已开始采用初步但新颖的治疗方法来治疗实验性甲状腺功能亢进症。
