Lung-resident innate lymphoid cells shows impact of age and dysbiosis on epigenetic and transcriptomic programming

The mechanisms underlying innate lymphoid cell (ILC) development and function in the neonatal lung remain incompletely defined. ILCs are critical mediators of early-life innate immune responses in the lung. Dysregulation of ILC homeostasis has both immediate and long-lasting effects on lung health. We generated single-cell transcriptomic and epigenetic datasets from the lungs of neonatal and young adult mice that includes subsets of type 1 (natural killer, NK cells) type 2 (ILC2) and type 3 (ILC3) cells. These datasets include mice subjected to early life antibiotic-induced dysbiosis, thereby modeling a common perturbation of the developing immune system in humans. Analysis of cell-cell communication and gene regulation in these datasets reveals underappreciated aspects of lung ILC biology, including marked interleukin-4 (IL-4) signaling in neonatal lung ILC2. This data represents a valuable resource for hypothesis generation regarding the molecular regulation of ILC gene expression and function in the neonatal lung.