Tissue repair requires temporal control of progenitor cell proliferation and differentiation to replenish damaged cells. In response to acute insult, group 3 innate lymphoid cells (ILC3s) regulate intestinal stem cell maintenance and subsequent tissue repair. ILC3-derived IL-22 is important for stem cell protection, but the mechanisms of ILC3-driven tissue regeneration remain incompletely defined. Here we report that ILC3-driven epithelial proliferation and tissue regeneration are independent of IL-22. In contrast, ILC3s amplify the magnitude of Hippo-Yap1 signaling in intestinal crypt cells, ensuring adequate initiation of tissue repair and preventing excessive pathology. Mechanistically, ILC3-driven tissue repair is Stat3 independent, but it involves activation of Src family kinases. Our findings reveal that ILC3-driven intestinal repair entails distinct transcriptional networks to control stem cell maintenance and epithelial regeneration, which implies that tissue repair and crypt proliferation can be influenced by targeting innate immune cells independent of the well-established effects of IL-22.

中文翻译：

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Yap1驱动的肠道修复受第3组先天淋巴样细胞控制。

组织修复需要暂时控制祖细胞的增殖和分化，以补充受损的细胞。为应对急性损伤，第3组先天淋巴样细胞（ILC3）调节肠道干细胞的维持和随后的组织修复。ILC3衍生的IL-22对于干细胞保护很重要，但ILC3驱动的组织再生机制仍未完全确定。在这里我们报告ILC3驱动的上皮细胞增殖和组织再生独立于IL-22。相比之下，ILC3s可放大肠道隐窝细胞中Hippo-Yap1信号的强度，从而确保组织修复的充分启动并防止过度病理。从机理上讲，ILC3驱动的组织修复是独立于Stat3的，但它涉及Src家族激酶的激活。