Tokushima University, Tokushima, Japan.
Department of Molecular Pathology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
Adv Exp Med Biol. 2024;1444:19-32. doi: 10.1007/978-981-99-9781-7_2.
One of the difficulties in studying the pathogenesis of autoimmune diseases is that the disease is multifactorial involving sex, age, MHC, environment, and some genetic factors. Because deficiency of Aire, a transcriptional regulator, is an autoimmune disease caused by a single gene abnormality, Aire is an ideal research target for approaching the enigma of autoimmunity, e.g., the mechanisms underlying Aire deficiency can be studied using genetically modified animals. Nevertheless, the exact mechanisms of the breakdown of self-tolerance due to Aire's dysfunction have not yet been fully clarified. This is due, at least in part, to the lack of information on the exact target genes controlled by Aire. State-of-the-art research infrastructures such as single-cell analysis are now in place to elucidate the essential function of Aire. The knowledge gained through the study of Aire-mediated tolerance should help our understanding of the pathogenesis of autoimmune disease in general.
研究自身免疫性疾病发病机制的困难之一在于，该病是多因素的，涉及性别、年龄、MHC、环境和一些遗传因素。由于转录调节因子 Aire 的缺乏是由单个基因异常引起的自身免疫性疾病，因此 Aire 是研究自身免疫之谜的理想研究目标，例如，可以使用基因修饰动物研究 Aire 缺乏的机制。然而，由于 Aire 功能障碍导致自身耐受破坏的确切机制尚未完全阐明。这至少部分是由于缺乏对 Aire 控制的精确靶基因的信息。单细胞分析等最先进的研究基础设施现在已经到位，可以阐明 Aire 的基本功能。通过研究 Aire 介导的耐受获得的知识应该有助于我们理解一般自身免疫性疾病的发病机制。
