先天性淋巴细胞
肿瘤坏死因子α
炎症
生物
免疫学
表皮生长因子
癌症研究
促炎细胞因子
细胞生物学
受体
先天免疫系统
免疫系统
生物化学
作者
Lei Zhou,Wenqing Zhou,Ann Mary Joseph,Coco Chu,Gregory G. Putzel,Beibei Fang,Fei Teng,Mengze Lv,Hiroshi Yano,Katrin I. Andreasson,Eisuke Mekada,Gérard Eberl,Gregory F. Sonnenberg
标识
DOI:10.1038/s41590-021-01110-0
摘要
Tumor necrosis factor (TNF) drives chronic inflammation and cell death in the intestine, and blocking TNF is a therapeutic approach in inflammatory bowel disease (IBD). Despite this knowledge, the pathways that protect the intestine from TNF are incompletely understood. Here we demonstrate that group 3 innate lymphoid cells (ILC3s) protect the intestinal epithelium from TNF-induced cell death. This occurs independent of interleukin-22 (IL-22), and we identify that ILC3s are a dominant source of heparin-binding epidermal growth factor–like growth factor (HB-EGF). ILC3s produce HB-EGF in response to prostaglandin E2 (PGE2) and engagement of the EP2 receptor. Mice lacking ILC3-derived HB-EGF exhibit increased susceptibility to TNF-mediated epithelial cell death and experimental intestinal inflammation. Finally, human ILC3s produce HB-EGF and are reduced from the inflamed intestine. These results define an essential role for ILC3-derived HB-EGF in protecting the intestine from TNF and indicate that disruption of this pathway contributes to IBD. TNF is an important driver of many inflammatory diseases. Zhou et al. demonstrate ILC3 production of the growth factor HB-EGF protects against TNF-mediated injury of the gut epithelium in inflammatory bowel disease.
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