Department of Immunology and Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Immunol Rev. 2016 May;271(1):38-55. doi: 10.1111/imr.12412.
The thymus consists of two distinct anatomical regions, the cortex and the medulla; medullary thymic epithelial cells (mTECs) play a crucial role in establishing central T-cell tolerance for self-antigens. Although the understanding of mTEC development in thymic organogenesis as well as the regulation of their differentiation and maturation has improved, the mechanisms of postnatal maintenance remain poorly understood. This issue has a central importance in immune homeostasis and physiological thymic involution as well as autoimmune disorders in various clinicopathological settings. Recently, several reports have demonstrated the existence of TEC stem or progenitor cells in the postnatal thymus, which are either bipotent or unipotent. We identified stem cells specified for mTEC-lineage that are generated in the thymic ontogeny and may sustain mTEC regeneration and lifelong central T-cell self-tolerance. This finding suggested that the thymic medulla is maintained autonomously by its own stem cells. Although several issues, including the relationship with other putative TEC stem/progenitors, remain unclear, further examination of mTEC stem cells (mTECSCs) and their regulatory mechanisms may contribute to the understanding of postnatal immune homeostasis. Possible relationships between decline of mTECSC activity and early thymic involution as well as various autoimmune disorders are discussed.
胸腺由两个不同的解剖区域组成，皮质和髓质；髓质胸腺上皮细胞（mTEC）在建立自身抗原的中枢 T 细胞耐受方面起着至关重要的作用。尽管人们对胸腺发生中的 mTEC 发育以及它们的分化和成熟的调控有了更好的理解，但对其出生后的维持机制仍知之甚少。这个问题在免疫稳态和生理性胸腺萎缩以及各种临床病理环境中的自身免疫性疾病中具有核心重要性。最近，有几项报道表明，在出生后的胸腺中存在 TEC 干细胞或祖细胞，它们具有双能或单能性。我们鉴定了在胸腺发生中产生的、针对 mTEC 谱系的干细胞，这些干细胞可能维持 mTEC 的再生和终生中枢 T 细胞自身耐受。这一发现表明，胸腺髓质是由其自身的干细胞自主维持的。尽管仍有一些问题尚不清楚，包括与其他假定的 TEC 干细胞/祖细胞的关系，但对 mTEC 干细胞（mTECSC）及其调控机制的进一步研究可能有助于理解出生后的免疫稳态。还讨论了 mTECSC 活性下降与早期胸腺萎缩以及各种自身免疫性疾病之间的可能关系。
