Innate lymphoid cells (ILCs) are generated early during ontogeny and persist predominantly as tissue-resident cells. Here, we examined how ILCs are maintained and renewed within tissues. We generated a single cell atlas of lung ILC2s and found that Il18r1⁺ ILCs comprise circulating and tissue-resident ILC progenitors (ILCP) and effector-cells with heterogeneous expression of the transcription factors Tcf7 and Zbtb16, and CD103. Our analyses revealed a continuous differentiation trajectory from Il18r1⁺ ST2⁻ ILCPs to Il18r⁻ ST2⁺ ILC2s, which was experimentally validated. Upon helminth infection, recruited and BM-derived cells generated the entire spectrum of ILC2s in parabiotic and shield chimeric mice, consistent with their potential role in the renewal of tissue ILC2s. Our findings identify local ILCPs and reveal ILCP in situ differentiation and tissue adaptation as a mechanism of ILC maintenance and phenotypic diversification. Local niches, rather than progenitor origin, or the developmental window during ontogeny, may dominantly imprint ILC phenotypes in adult tissues.

先天淋巴样细胞 (ILC) 在个体发育早期产生，并主要作为组织驻留细胞持续存在。在这里，我们研究了 ILC 如何在组织内维持和更新。我们生成了肺 ILC2 的单细胞图谱，发现 Il18r1 ⁺ ILC 包含循环和组织驻留的 ILC 祖细胞 (ILCP) 和具有转录因子 Tcf7 和 Zbtb16 以及 CD103 异质表达的效应细胞。^{我们的分析揭示了从 Il18r1 +} ST2 ⁻ ILCP 到 Il18r ⁻ ST2 ⁺ ILC2 的连续分化轨迹，并经过实验验证。蠕虫感染后，募集的细胞和 BM 衍生的细胞在共生和屏蔽嵌合小鼠中产生了整个 ILC2 谱，这与它们在组织 ILC2 更新中的潜在作用一致。我们的研究结果确定了局部 ILCP，并揭示了 ILCP原位分化和组织适应是 ILC 维持和表型多样化的机制。局部生态位，而不是祖细胞起源，或个体发育过程中的发育窗口，可能在成体组织中占主导地位地印记 ILC 表型。