Title | Group 3 innate lymphoid cells produce the growth factor HB-EGF to protect the intestine from TNF-mediated inflammation. |
Publication Type | Journal Article |
Year of Publication | 2022 |
Authors | Zhou L, Zhou W, Joseph AM, Chu C, Putzel GG, Fang B, Teng F, Lyu M, Yano H, Andreasson KI, Mekada E, Eberl G, Sonnenberg GF |
Journal | Nat Immunol |
Date Published | 2022 Jan 31 |
ISSN | 1529-2916 |
Abstract | 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. |
DOI | 10.1038/s41590-021-01110-0 |
Alternate Journal | Nat Immunol |
PubMed ID | 35102343 |
Grant List | R01AI123368 / / Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) / R01AI145989 / / Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) / R01AI162936 / / Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) / T32DK116970 / / Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) / 608975 / / Crohn's and Colitis Foundation (Crohn's & Colitis Foundation) / 831404 / / Crohn's and Colitis Foundation (Crohn's & Colitis Foundation) / |