Semwal Manpreet K, Jones Nicholas E, Griffith Ann V
Department of Microbiology, Immunology and Molecular Genetics, University of Texas Joe R. and Teresa Lozano Long School of Medicine, UT Health San Antonio, San Antonio, TX, United States.
Front Immunol. 2021 Mar 3;12:636072. doi: 10.3389/fimmu.2021.636072. eCollection 2021.
The thymus is the primary site of T lymphocyte development, where mutually inductive signaling between lymphoid progenitors and thymic stromal cells directs the progenitors along a well-characterized program of differentiation. Although thymic stromal cells, including thymic epithelial cells (TECs) are critical for the development of T cell-mediated immunity, many aspects of their basic biology have been difficult to resolve because they represent a small fraction of thymus cellularity, and because their isolation requires enzymatic digestion that induces broad physiological changes. These obstacles are especially relevant to the study of metabolic regulation of cell function, since isolation procedures necessarily disrupt metabolic homeostasis. In contrast to the well-characterized relationships between metabolism and intracellular signaling in T cell function during an immune response, metabolic regulation of thymic stromal cell function represents an emerging area of study. Here, we review recent advances in three distinct, but interconnected areas: regulation of mTOR signaling, reactive oxygen species (ROS), and autophagy, with respect to their roles in the establishment and maintenance of the thymic stromal microenvironment.
胸腺是T淋巴细胞发育的主要场所，在那里淋巴祖细胞与胸腺基质细胞之间的相互诱导信号沿着一个特征明确的分化程序引导祖细胞分化。尽管包括胸腺上皮细胞（TECs）在内的胸腺基质细胞对T细胞介导的免疫发育至关重要，但其基本生物学的许多方面一直难以解析，因为它们在胸腺细胞组成中只占一小部分，而且其分离需要酶消化，这会引发广泛的生理变化。这些障碍对于细胞功能代谢调节的研究尤为重要，因为分离程序必然会破坏代谢稳态。与免疫反应期间T细胞功能中代谢与细胞内信号传导之间已明确的关系不同，胸腺基质细胞功能的代谢调节是一个新兴的研究领域。在此，我们综述了三个不同但相互关联领域的最新进展：mTOR信号传导、活性氧（ROS）和自噬的调节，及其在胸腺基质微环境建立和维持中的作用。
