Sunnybrook Research Institute, Toronto, Ontario M4N 3M5, Canada; and.
Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
J Immunol. 2021 Jan 15;206(2):249-256. doi: 10.4049/jimmunol.2000889.
The thymus is an intricate primary lymphoid organ, wherein bone marrow-derived lymphoid progenitor cells are induced to develop into functionally competent T cells that express a diverse TCR repertoire, which is selected to allow for the recognition of foreign Ags while avoiding self-reactivity or autoimmunity. Thymus stromal cells, which can include all non-T lineage cells, such as thymic epithelial cells, endothelial cells, mesenchymal/fibroblast cells, dendritic cells, and B cells, provide signals that are essential for thymocyte development as well as for the homeostasis of the thymic stroma itself. In this brief review, we focus on the key roles played by thymic stromal cells during early stages of T cell development, such as promoting the homing of thymic-seeding progenitors, inducing T lineage differentiation, and supporting thymocyte survival and proliferation. We also discuss recent advances on the transcriptional regulation that govern thymic epithelial cell function as well as the cellular and molecular changes that are associated with thymic involution and regeneration.
胸腺是一个复杂的初级淋巴器官，其中骨髓源性淋巴祖细胞被诱导发育成具有功能性的成熟 T 细胞，这些细胞表达多样化的 TCR 库，以允许识别外来抗原，同时避免自身反应或自身免疫。胸腺基质细胞，包括所有非 T 细胞谱系细胞，如胸腺上皮细胞、内皮细胞、间充质/成纤维细胞、树突状细胞和 B 细胞，提供了对胸腺细胞发育以及胸腺基质自身稳态至关重要的信号。在这篇简要综述中，我们重点关注了胸腺基质细胞在 T 细胞发育早期阶段所发挥的关键作用，如促进胸腺定植前体的归巢、诱导 T 细胞谱系分化，以及支持胸腺细胞的存活和增殖。我们还讨论了关于转录调控的最新进展，这些调控决定了胸腺上皮细胞的功能，以及与胸腺萎缩和再生相关的细胞和分子变化。
