Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Immunity. 2013 Apr 18;38(4):694-704. doi: 10.1016/j.immuni.2012.12.003.
Group 2 innate lymphoid cells (ILC2) are innate lymphocytes that confer protective type 2 immunity during helminth infection and are also involved in allergic airway inflammation. Here we report that ILC2 development required T cell factor 1 (TCF-1, the product of the Tcf7 gene), a transcription factor also implicated in T cell lineage specification. Tcf7(-/-) mice lack ILC2, and were unable to mount ILC2-mediated innate type 2 immune responses. Forced expression of TCF-1 in bone marrow progenitors partially bypassed the requirement for Notch signaling in the generation of ILC2 in vivo. TCF-1 acted through both GATA-3-dependent and GATA-3-independent pathways to promote the generation of ILC2. These results are reminiscent of the critical roles of TCF-1 in early T cell development. Hence, transcription factors that underlie early steps of T cell development are also implicated in the development of innate lymphoid cells.
2 型固有淋巴细胞(ILC2)是固有淋巴细胞,在寄生虫感染期间赋予保护性 2 型免疫,并且还参与过敏性气道炎症。在这里,我们报告 ILC2 的发育需要 T 细胞因子 1(TCF-1,Tcf7 基因的产物),这是一种转录因子,也与 T 细胞谱系特异性有关。Tcf7(-/-)小鼠缺乏 ILC2,并且无法引发 ILC2 介导的固有 2 型免疫反应。在骨髓祖细胞中强制表达 TCF-1 部分绕过了 Notch 信号在体内产生 ILC2 中的要求。TCF-1 通过 GATA-3 依赖性和 GATA-3 非依赖性途径发挥作用,以促进 ILC2 的产生。这些结果使人联想到 TCF-1 在早期 T 细胞发育中的关键作用。因此,构成 T 细胞发育早期步骤的转录因子也与固有淋巴细胞的发育有关。