Department of Immunology, The University of Texas Southwestern Medical Center, Dallas, TX, United States.
Department of Microbiology, Immunology & Genetics, The University of North Texas Health Sciences Center, Fort Worth, TX, United States.
Front Immunol. 2022 Jun 10;13:864777. doi: 10.3389/fimmu.2022.864777. eCollection 2022.
The thymus, a primary lymphoid organ, produces the T cells of the immune system. Originating from the 3 pharyngeal pouch during embryogenesis, this organ functions throughout life. Yet, thymopoiesis can be transiently or permanently damaged contingent on the types of systemic stresses encountered. The thymus also undergoes a functional decline during aging, resulting in a progressive reduction in naïve T cell output. This atrophy is evidenced by a deteriorating thymic microenvironment, including, but not limited, epithelial-to-mesenchymal transitions, fibrosis and adipogenesis. An exploration of cellular changes in the thymus at various stages of life, including mouse models of in-born errors of immunity and with single cell RNA sequencing, is revealing an expanding number of distinct cell types influencing thymus functions. The thymus microenvironment, established through interactions between immature and mature thymocytes with thymus epithelial cells (TEC), is well known. Less well appreciated are the contributions of neural crest cell-derived mesenchymal cells, endothelial cells, diverse hematopoietic cell populations, adipocytes, and fibroblasts in the thymic microenvironment. In the current review, we will explore the contributions of the many stromal cell types participating in the formation, expansion, and contraction of the thymus under normal and pathophysiological processes. Such information will better inform approaches for restoring thymus functionality, including thymus organoid technologies, beneficial when an individuals' own tissue is congenitally, clinically, or accidentally rendered non-functional.
胸腺是初级淋巴器官，产生免疫系统的 T 细胞。它起源于胚胎发生过程中的 3 个咽囊，在整个生命过程中发挥作用。然而，根据所遇到的系统性压力的类型，胸腺发生可以暂时或永久受损。胸腺在衰老过程中也会经历功能下降，导致幼稚 T 细胞输出逐渐减少。这种萎缩的证据是胸腺微环境恶化，包括但不限于上皮-间充质转化、纤维化和脂肪生成。对生命各个阶段胸腺中细胞变化的探索，包括先天免疫错误的小鼠模型和单细胞 RNA 测序，揭示了越来越多的不同细胞类型影响胸腺功能。胸腺微环境是通过未成熟和成熟的胸腺细胞与胸腺上皮细胞（TEC）之间的相互作用建立的，这一点广为人知。不太为人所知的是神经嵴细胞衍生的间充质细胞、内皮细胞、各种造血细胞群体、脂肪细胞和成纤维细胞在胸腺微环境中的贡献。在当前的综述中，我们将探讨许多参与正常和病理生理过程中胸腺形成、扩张和收缩的基质细胞类型的贡献。这些信息将更好地为恢复胸腺功能的方法提供信息，包括胸腺类器官技术，当个体自身的组织因先天、临床或意外原因而无法正常工作时，这种技术非常有益。
