Among the features that distinguish type 1 innate lymphoid cells (ILC1s) from natural killer (NK) cells is a gene signature indicative of 'imprinting' by cytokines of the TGF-β family. We studied mice in which ILC1s and NK cells lacked SMAD4, a signal transducer that facilitates the canonical signaling pathway common to all cytokines of the TGF-β family. While SMAD4 deficiency did not affect ILC1 differentiation, NK cells unexpectedly acquired an ILC1-like gene signature and were unable to control tumor metastasis or viral infection. Mechanistically, SMAD4 restrained non-canonical TGF-β signaling mediated by the cytokine receptor TGFβR1 in NK cells. NK cells from a SMAD4-deficient person affected by polyposis were also hyper-responsive to TGF-β. These results identify SMAD4 as a previously unknown regulator that restricts non-canonical TGF-β signaling in NK cells.

中文翻译：

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SMAD4通过减少非经典的TGF-β信号传导来阻止NK细胞向ILC1样细胞的转化。

在将1型先天淋巴样细胞（ILC1s）与自然杀伤（NK）细胞区分开的特征中，有一个基因标志表明TGF-β家族的细胞因子“烙印”。我们研究了其中ILC1s和NK细胞缺少SMAD4的小鼠，SMAD4是一种信号转导子，可促进TGF-β家族所有细胞因子共有的规范信号通路。虽然SMAD4缺乏症不会影响ILC1分化，但NK细胞出乎意料地获得了ILC1样基因标记，无法控制肿瘤转移或病毒感染。从机制上讲，SMAD4抑制了NK细胞中细胞因子受体TGFβR1介导的非经典TGF-β信号传导。来自息肉病影响的SMAD4缺陷型人的NK细胞对TGF-β也有高反应性。