In Situ Maturation and Tissue Adaptation of Type 2 Innate Lymphoid Cell Progenitors

We analyzed the full spectrum of lung ILC2s at single-cell transcriptome resolution and identified an immature population of Il18r1+ tissue-associated ILCs, that express Tcf7 and Zbtb16, transcription factors known to act in ILC progenitors, and low levels of Gata3, ST2 and ILC2 effector molecules. We revealed a continuous differentiation trajectory and validated the potential of immature Il18r1+ cells to differentiate into Gata3hi ILC2s. We found that immature ILCs were recruited into the adult lung of parabiotic and shield chimeric mice during helminth infection. Intriguingly, recruited cells generated the entire spectrum of ILC2s in the lung, consistent with their potential role in the renewal of tissue ILC2s. Our work identifies local ILC progenitors and highlights their tissue adaptation and in situ differentiation as a mechanism of ILC maintenance and phenotypic diversification Comprehensive single-cell atlas and transcriptome comparison of ILC populations in the BM(Lin-IL18r1+Icos+), and neonatal(liveLin-CD45+Thy1+IL7r+Nk1.1-ST2+/-) and adult lung (LiveLin-CD45+Thy1+IL7r+Nk1.1-) at steady-state, as well as over the course of helminth infection in wild-type, parabiotic and shield chimeric mice,