The role of the autoimmune regulator (Aire) in central immune tolerance and thymic self-representation was first described more than 20 years ago, but fascinating new insights into its biology continue to emerge, particularly in the era of advanced single-cell genomics. We briefly describe the role of human genetics in the discovery of Aire, as well as insights into its function gained from genotype–phenotype correlations and the spectrum of Aire-associated autoimmunity—including insights from patients with Aire mutations with broad and diverse implications for human health. We then highlight emerging trends in Aire biology, focusing on three topic areas. First, we discuss medullary thymic epithelial diversity and the role of Aire in thymic epithelial development. Second, we highlight recent developments regarding the molecular mechanisms of Aire and its binding partners. Finally, we describe the rapidly evolving biology of the identity and function of extrathymic Aire-expressing cells (eTACs), and a novel eTAC subset called Janus cells, as well as their potential roles in immune homeostasis.Expected final online publication date for the Annual Review of Immunology, Volume 42 is April 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

中文翻译：

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艾尔自身免疫

自身免疫调节因子 (Aire) 在中枢免疫耐受和胸腺自我表达中的作用于 20 多年前首次被描述，但对其生物学的令人着迷的新见解不断出现，特别是在先进的单细胞基因组学时代。我们简要描述了人类遗传学在 Aire 发现中的作用，以及从基因型-表型相关性和 Aire 相关自身免疫谱中获得的对其功能的见解，包括来自对人类具有广泛而多样影响的 Aire 突变患者的见解健康。然后，我们重点介绍艾尔生物学的新兴趋势，重点关注三个主题领域。首先，我们讨论髓质胸腺上皮多样性和 Aire 在胸腺上皮发育中的作用。其次，我们重点介绍了 Aire 及其结合伙伴的分子机制的最新进展。最后，我们描述了胸腺外 Aire 表达细胞 (eTAC) 的身份和功能的快速进化生物学，以及称为 Janus 细胞的新型 eTAC 子集，以及它们在免疫稳态中的潜在作用。年度报告的预计最终在线出版日期《免疫学评论》第 42 卷发布日期为 2024 年 4 月。请参阅 http://www.annualreviews.org/page/journal/pubdates 了解修订后的估计值。