Layered ontogeny and in situ perinatal priming of tissue ILC2s

The perinatal period is a critical window for the distribution of innate tissue-resident immune cells to developing organs. Despite epidemiologic evidence implicating early life environment in risk for allergy, temporally controlled lineage-tracing of ILC2s during this period has not been done. Using complementary fate-mapping approaches and fluorescent reporters of ILC2 activation, we demonstrate that ILC2s appear in multiple organs during late gestation similar to tissue macrophages, but unlike the latter, a majority of peripheral ILC2 pools are generated de novo during a postnatal window. This period was accompanied by systemic ILC2 priming and acquisition of tissue-specific expression profiles. Although perinatal ILC2s are variably replaced with age, the dramatic increases in tissue ILC2s following helminth infection are mediated through local expansion independent of de novo generation by BM hematopoiesis. We provide the first comprehensive temporally controlled fate-mapping of an innate lymphocyte subset with notable nuances as compared to tissue macrophage ontogeny single-cell mRNA profiles of ILC2s sorted from neonatal (14-day-old) mouse lung and skin tissues