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Zeis, Patrice; Lian, Mi; Fan, Xiying; Herman, Josip S.; Hernandez, Daniela C.; Gentek, Rebecca; Elias, Shlomo; Symowski, Cornelia; Knöpper, Konrad; Peltokangas, Nina; Friedrich, Christin; Doucet-Ladeveze, Remi; Kabat, Agnieszka M.; Locksley, Richard M.; Voehringer, David; Bajenoff, Marc; Rudensky, Alexander Y.; Romagnani, Chiara; Grün, Dominic; Gasteiger, Georg
Immunity, 10/2020, Volume: 53, Issue: 4Journal Article
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. Display omitted •A single-cell atlas of BM ILCs and lung ILCs of healthy, infected, and parabiotic mice•Identification of tissue-associated ILC progenitors in neonatal and adult lung•Cells recruited from BM generate the entire spectrum of ILC2s in infected lungs•Local cues imprint the phenotypes of ILC2s differentiating in the adult lung To investigate how innate lymphoid cells (ILCs) are locally maintained, Zeis et al. generated a single-cell atlas of lung ILCs and tracked Il18r1+ progenitor and effector ILC2s. Their work identifies tissue-resident and circulating ILC progenitors and highlights in situ differentiation and tissue adaptation as a mechanism of ILC renewal and phenotypic diversification.
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