Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Department of Microbiology and Immunology School of Medicine, Jiangsu Provincial Key Laboratory of Critical Care Medicine, Southeast University, Nanjing, Jiangsu 210009, China.
Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Department of Immunology & Kidney Cancer Program, Harold C. Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Cell Rep. 2023 Aug 29;42(8):112924. doi: 10.1016/j.celrep.2023.112924. Epub 2023 Aug 3.
Lymphoid tissue inducer (LTi) cells, a subset of innate lymphoid cells (ILCs), play an essential role in the formation of secondary lymphoid tissues. However, the regulation of the development and functions of this ILC subset is still elusive. In this study, we report that the transcription factor T cell factor 1 (TCF-1), just as GATA3, is indispensable for the development of non-LTi ILC subsets. While LTi cells are still present in TCF-1-deficient mice, the organogenesis of Peyer's patches (PPs), but not of lymph nodes, is impaired in these mice. LTi cells from different tissues have distinct gene expression patterns, and TCF-1 regulates the expression of lymphotoxin specifically in PP LTi cells. Mechanistically, TCF-1 may directly and/or indirectly regulate Lta, including through promoting the expression of GATA3. Thus, the TCF-1-GATA3 axis, which plays an important role during T cell development, also critically regulates the development of non-LTi cells and tissue-specific functions of LTi cells.
淋巴组织诱导细胞（LTi）是先天淋巴样细胞（ILC）的一个亚群，在次级淋巴组织的形成中发挥着重要作用。然而，这个 ILC 亚群的发育和功能的调节仍然难以捉摸。在这项研究中，我们报告转录因子 T 细胞因子 1（TCF-1）与 GATA3 一样，对于非 LTi ILC 亚群的发育是必不可少的。虽然 LTi 细胞仍然存在于 TCF-1 缺陷小鼠中，但这些小鼠的派尔集合淋巴结（PP）的器官发生而不是淋巴结的器官发生受损。来自不同组织的 LTi 细胞具有不同的基因表达模式，并且 TCF-1 特异性地调节 PP LTi 细胞中淋巴毒素的表达。从机制上讲，TCF-1 可能直接和/或间接调节 Lta，包括通过促进 GATA3 的表达。因此，在 T 细胞发育过程中发挥重要作用的 TCF-1-GATA3 轴也严格调节非 LTi 细胞的发育和 LTi 细胞的组织特异性功能。
