Prenatal inflammation remodels lung immunity and function by programming ILC2 hyperactivation.

Here, we examine how prenatal inflammation shapes tissue function and immunity in the lung by reprogramming tissue-resident immune cells from early development. Maternal, but not fetal, type I interferon-mediated inflammation provokes expansion and hyperactivation of group 2 innate lymphoid cells (ILC2s) seeding the developing lung. Hyperactivated ILC2s produce increased IL-5 and IL-13 and are associated with acute Th2 bias, decreased Tregs, and persistent lung eosinophilia into adulthood.

Prenatal inflammation reprograms hyperactive ILC2s that promote allergic lung inflammation and airway dysfunction.

Unlabelled: Allergic asthma is a chronic respiratory disease that initiates in early life, but causal mechanisms are poorly understood. Here we examined how prenatal inflammation shapes allergic asthma susceptibility by reprogramming lung immunity from early development. Induction of Type I interferon-mediated inflammation during development provoked expansion and hyperactivation of group 2 innate lymphoid cells (ILC2s) seeding the developing lung.