A set of immune-regulating cells, ILC3s, produce heparin-binding epidermal growth factor–like growth factor (HB-EGF) in response to gut inflammation. Although these immune cells reside in the intestines, their numbers are known to be depleted in the inflamed intestines of IBD patients. HB-EGF was found to counter the harmful effects of, and protect the intestine from, inflammation mediated by tumor necrosis factor (TNF).