Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA.
Laboratory of Clinical Immunology & Microbiology, National Institute of Allergy & Infectious Diseases (NIAID), NIH, Bethesda, MD 20892, USA.
Curr Opin Immunol. 2017 Dec;49:71-78. doi: 10.1016/j.coi.2017.10.003. Epub 2017 Oct 21.
AIRE is a well-established master regulator of central tolerance. It plays an essential role in driving expression of tissue-specific antigens in the thymus and shaping the development of positively selected T-cells. Humans and mice with compromised or absent AIRE function have markedly variable phenotypes that include a range of autoimmune manifestations. Recent evidence suggests that this variability stems from cooperation of autoimmune susceptibilities involving both central and peripheral tolerance checkpoints. Here we discuss the broadening understanding of the factors that influence Aire expression, modify AIRE function, and the impact and intersection of AIRE with peripheral immunity. This rapidly expanding body of knowledge will force a reexamination of the definition and clinical management of APS-1 patients as well as provide a foundation for the development of immunomodulatory strategies targeting central tolerance.
AIRE 是一种成熟的中枢耐受主要调控因子。它在驱动胸腺组织特异性抗原的表达和塑造阳性选择 T 细胞的发育方面发挥着重要作用。AIRE 功能受损或缺失的人类和小鼠表现出明显不同的表型，包括一系列自身免疫表现。最近的证据表明，这种可变性源于涉及中枢和外周耐受检查点的自身免疫易感性的合作。在这里，我们讨论了影响 Aire 表达、修饰 AIRE 功能的因素，以及 AIRE 与外周免疫的相互作用和影响。这一快速发展的知识体系将迫使我们重新审视 APS-1 患者的定义和临床管理，并为针对中枢耐受的免疫调节策略的发展提供基础。
