2. Academic Validation
  3. Group 3 innate lymphoid cells produce the growth factor HB-EGF to protect the intestine from TNF-mediated inflammation

Group 3 innate lymphoid cells produce the growth factor HB-EGF to protect the intestine from TNF-mediated inflammation

  • Nat Immunol. 2022 Feb;23(2):251-261. doi: 10.1038/s41590-021-01110-0.
Lei Zhou 1 2 3,  Wenqing Zhou 4 5 6,  Ann M Joseph 4 5 6,  Coco Chu 6,  Gregory G Putzel 6,  Beibei Fang 7,  Fei Teng 4 5 6,  Mengze Lyu 4 5 6,  Hiroshi Yano 6,  Katrin I Andreasson 8,  Eisuke Mekada 9,  Gerard Eberl 10,  Gregory F Sonnenberg 11 12 13
Affiliations

Affiliations

  • 1 Joan and Sanford I. Weill Department of Medicine, Division of Gastroenterology, Weill Cornell Medicine, New York, NY, USA. [email protected].
  • 2 Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY, USA. [email protected].
  • 3 Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY, USA. [email protected].
  • 4 Joan and Sanford I. Weill Department of Medicine, Division of Gastroenterology, Weill Cornell Medicine, New York, NY, USA.
  • 5 Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY, USA.
  • 6 Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY, USA.
  • 7 Immunology and Microbial Pathogenesis Program, Graduate School of Medical Sciences, Weill Cornell Medicine, New York, NY, USA.
  • 8 Department of Neurology & Neurological Sciences, Stanford Neuroscience Institute, Stanford Immunology Program, Stanford School of Medicine, Stanford, CA, USA.
  • 9 Department of Cell Biology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
  • 10 Microenvironment and Immunity Unit, Institut Pasteur, Paris, France.
  • 11 Joan and Sanford I. Weill Department of Medicine, Division of Gastroenterology, Weill Cornell Medicine, New York, NY, USA. [email protected].
  • 12 Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY, USA. [email protected].
  • 13 Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY, USA. [email protected].
PMID: 35102343 DOI: 10.1038/s41590-021-01110-0
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.

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