Division of Molecular Immunology, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3052, Australia;
J Immunol. 2013 Oct 15;191(8):4383-91. doi: 10.4049/jimmunol.1301228. Epub 2013 Sep 13.
Innate lymphocyte populations play a central role in conferring protective immunity at the mucosal frontier. In this study, we demonstrate that T cell factor 1 (TCF-1; encoded by Tcf7), a transcription factor also important for NK and T cell differentiation, is expressed by multiple innate lymphoid cell (ILC) subsets, including GATA3(+) nuocytes (ILC2) and NKp46(+) ILCs (ILC3), which confer protection against lung and intestinal inflammation. TCF-1 was intrinsically required for the differentiation of both ILC2 and NKp46(+) ILC3. Loss of TCF-1 expression impaired the capacity of these ILC subsets to produce IL-5, IL-13, and IL-22 and resulted in crippled responses to intestinal infection with Citrobacter rodentium. Furthermore, a reduction in T-bet expression required for Notch-2-dependent development of NKp46(+) ILC3 showed a dose-dependent reduction in TCF-1 expression. Collectively, our findings demonstrate an essential requirement for TCF-1 in ILC2 differentiation and reveal a link among Tcf7, Notch, and Tbx21 in NKp46(+) ILC3 development.
固有淋巴细胞群体在黏膜前沿赋予保护性免疫方面发挥着核心作用。在这项研究中，我们证明了转录因子 T 细胞因子 1（TCF-1；由 Tcf7 编码），对于 NK 和 T 细胞分化也很重要，它由多个固有淋巴细胞（ILC）亚群表达，包括 GATA3（+）nuocytes（ILC2）和 NKp46（+）ILC（ILC3），它们赋予了针对肺部和肠道炎症的保护作用。TCF-1 对于 ILC2 和 NKp46（+）ILC3 的分化都是内在必需的。TCF-1 表达的缺失损害了这些 ILC 亚群产生 IL-5、IL-13 和 IL-22 的能力，并导致对柠檬酸杆菌肠道感染的反应受损。此外，对于 Notch-2 依赖性 NKp46（+）ILC3 发育所需的 T-bet 表达的减少显示出 TCF-1 表达的剂量依赖性减少。总之，我们的研究结果表明 TCF-1 是 ILC2 分化所必需的，并揭示了 Tcf7、Notch 和 Tbx21 在 NKp46（+）ILC3 发育中的联系。
