Group 2 innate lymphoid cells prevent endotoxin-induced fetal demise
Group 2 innate lymphoid cells (ILC2s) produce type-2 cytokines and play key roles in the tissues they populate. They are involved in infection, inflammatory pathology, metabolism and homeostasis in gut, lung, skin and adipose tissue. Here we show that mouse ILC2s in the uterus co-localise with IL-33 producing stromal cells, constitutively produce IL-5 and amphiregulin, and display tissue-specific gene signatures that change with pregnancy. The uterus of ILC2-deficient mice had decreased numbers of eosinophils, reduced expression of Il4, Il5 and Il13, and genes associated with alternative activation of macrophages and dendritic cells. Although this reduction in the type-2 environment did not impact on fetal survival in healthy ILC2-deficient mice, bacterial endotoxin challenge during pregnancy led to pronounced embryo resorption that correlated with an inability to control type-1 inflammatory cytokines. These results indicate that ILC2s are key regulators of type-2 immunity in the uterus and are required to maintain immune homeostasis during pregnancy.