Tissue-resident innate lymphoid cells (ILCs) play a vital role in the frontline defense of various tissues, including the lung. The development of type 2 ILCs (ILC2s) depends on transcription factors such as GATA3, RORα, GFI1, and Bcl11b; however, the factors regulating lung-resident ILC2s remain unclear. Through fate mapping analysis of the paralog transcription factors GFI1 and GFI1B, we show that GFI1 is consistently expressed during the transition from progenitor to mature ILC2s. In contrast, GFI1B expression is limited to specific subsets of bone marrow progenitors and lung-resident ILC progenitors. We found that GFI1B + lung ILC progenitors represent a multi-lineage subset with tissue-resident characteristics and the potential to form lung-derived ILC subsets and liver-resident ILC1s. Loss of GFI1B in bone marrow progenitors led to the selective loss of lung-resident IL-18R + ILCs and mature ILC2, subsequently preventing the emergence of effector ILCs that could protect the lung against inflammatory or tumor challenge.

中文翻译：

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GFI1B 明确了肺部先天淋巴细胞祖细胞的发育潜力


组织驻留先天淋巴细胞 (ILC) 在包括肺在内的各种组织的前线防御中发挥着至关重要的作用。 2型ILC（ILC2）的发育依赖于GATA3、RORα、GFI1和Bcl11b等转录因子；然而，调节肺驻留 ILC2 的因素仍不清楚。通过对旁系同源转录因子 GFI1 和 GFI1B 的命运图谱分析，我们发现 GFI1 在从祖细胞向成熟 ILC2 的转变过程中持续表达。相反，GFI1B 表达仅限于骨髓祖细胞和肺驻留 ILC 祖细胞的特定亚群。我们发现 GFI1B + 肺 ILC 祖细胞代表了具有组织驻留特征的多谱系子集，并且有可能形成肺源性 ILC 子集和肝驻留性 ILC1。骨髓祖细胞中 GFI1B 的缺失导致肺部驻留的 IL-18R + ILC 和成熟 ILC2 的选择性缺失，随后阻止了可以保护肺部免受炎症或肿瘤攻击的效应 ILC 的出现。