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起作用的机制预防自身免疫性疾病，包括阳性和阴性选择以及调节性T细胞（Tregs）的产生。从胸腺穿过血管周间隙（PVS）到达血液是另一个可能的检查点，如某些自身免疫/免疫缺陷综合症所示。在多基因自身免疫性疾病中，细微的胸腺功能障碍可能加重遗传，激素和环境方面的提示。在这里，我们涵盖（a）诱导耐受性的细胞类型，无论是胸腺上皮细胞还是簇状细胞，还是树突状，B或胸腺肌样细胞；（b）与胸腺解剖区室有关的耐受诱导机制及其失败，并特别着重于人类单基因和多基因自身免疫性疾病以及相关的胸腺病理学（如果已知）；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）和从胸腺流出（例如MTS1，CORO1A）；（d）重症肌无力是发炎或失调的赘生性“胸腺病”的原型结果。