Program in Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
Adv Exp Med Biol. 2022;1365:25-39. doi: 10.1007/978-981-16-8387-9_3.
The thymus provides a microenvironment conducive to the differentiation of innate lymphoid cells (ILCs), supplying IL-7 as well as Notch ligands. Early T cell precursors also express a number of obligatory transcription factors essential for ILC differentiation. Therefore, the thymus could be a powerhouse for ILC production. However, coordinated regulation by transcription factors and T cell receptor signaling events ensure that T cell production is the dominating output of the thymus. One group of the key regulators are the basic helix-loop-helix E protein transcription factors and their inhibitors, Id proteins. When E protein activities are downregulated, T cell development is blocked and massive ILC2 production occurs in the thymus. Normally, the thymus indeed generates a small number of ILCs, mostly group 2 ILCs (ILC2s). It has been shown in vitro that ILC2s can be differentiated from multipotent early T cell progenitors (ETPs) as well as committed T cell precursors. Moreover, thymus-derived ILC precursors have been found in the blood of adult mice. They then home to peripheral tissues and undergo differentiation into distinct ILC subsets. These ILC precursors may replenish tissue ILC pools in steady state or on demand in pathophysiological conditions. Collectively, emerging evidence suggests that the thymus plays an underappreciated role in ILC homeostasis.
胸腺为先天淋巴细胞（ILC）的分化提供了有利的微环境，提供 IL-7 以及 Notch 配体。早期 T 细胞前体也表达许多对 ILC 分化必不可少的必需转录因子。因此，胸腺可能是 ILC 产生的动力源。然而，转录因子和 T 细胞受体信号事件的协调调节确保了 T 细胞的产生是胸腺的主要输出。一组关键的调节因子是碱性螺旋-环-螺旋 E 蛋白转录因子及其抑制剂，Id 蛋白。当 E 蛋白活性被下调时，T 细胞发育受阻，大量 ILC2 在胸腺中产生。正常情况下，胸腺确实会产生少量 ILC，主要是 2 型 ILC（ILC2）。体外研究表明，ILC2 可从多能早期 T 细胞祖细胞（ETP）以及定向 T 细胞前体分化而来。此外，在成年小鼠的血液中发现了来自胸腺的 ILC 前体。然后，它们归巢到外周组织，并分化为不同的 ILC 亚群。这些 ILC 前体可能在稳态或病理生理条件下补充组织 ILC 池。总的来说，新出现的证据表明，胸腺在 ILC 稳态中起着被低估的作用。
