Institute of Pathology, University Medical Centre Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, 606-8507, Japan.
Semin Immunopathol. 2021 Feb;43(1):45-64. doi: 10.1007/s00281-021-00842-3. Epub 2021 Feb 3.
The thymus prevents autoimmune diseases through mechanisms that operate in the cortex and medulla, comprising positive and negative selection and the generation of regulatory T-cells (Tregs). Egress from the thymus through the perivascular space (PVS) to the blood is another possible checkpoint, as shown by some autoimmune/immunodeficiency syndromes. In polygenic autoimmune diseases, subtle thymic dysfunctions may compound genetic, hormonal and environmental cues. Here, we cover (a) tolerance-inducing cell types, whether thymic epithelial or tuft cells, or dendritic, B- or thymic myoid cells; (b) tolerance-inducing mechanisms and their failure in relation to thymic anatomic compartments, and with special emphasis on human monogenic and polygenic autoimmune diseases and the related thymic pathologies, if known; (c) polymorphisms and mutations of tolerance-related genes with an impact on positive selection (e.g. the gene encoding the thymoproteasome-specific subunit, PSMB11), promiscuous gene expression (e.g. AIRE, PRKDC, FEZF2, CHD4), Treg development (e.g. SATB1, FOXP3), T-cell migration (e.g. TAGAP) and egress from the thymus (e.g. MTS1, CORO1A); (d) myasthenia gravis as the prototypic outcome of an inflamed or disordered neoplastic 'sick thymus'.
胸腺通过在皮质和髓质中发挥作用的机制来预防自身免疫性疾病，这些机制包括阳性和阴性选择以及调节性 T 细胞（Treg）的产生。通过血管周围空间（PVS）从胸腺中流出到血液是另一个可能的检查点，正如一些自身免疫/免疫缺陷综合征所表明的那样。在多基因自身免疫性疾病中，微妙的胸腺功能障碍可能会加剧遗传、激素和环境线索。在这里，我们涵盖了（a）诱导耐受的细胞类型，无论是胸腺上皮细胞还是簇细胞，还是树突状细胞、B 细胞或胸腺肌样细胞；（b）诱导耐受的机制及其与胸腺解剖区室的失败，以及特别强调人类单基因和多基因自身免疫性疾病和相关的胸腺病理学，如果已知的话；（c）与阳性选择（例如编码胸腺蛋白酶体特异性亚基的基因，PSMB11）、混杂基因表达（例如 AIRE、PRKDC、FEZF2、CHD4）、Treg 发育（例如 SATB1、FOXP3）、T 细胞迁移（例如 TAGAP）和从胸腺中流出（例如 MTS1、CORO1A）相关的耐受相关基因的多态性和突变；（d）重症肌无力作为发炎或紊乱的肿瘤“病态胸腺”的典型结果。
