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

Overview

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.

publication date

  • January 31, 2022

Research

keywords

  • Heparin-binding EGF-like Growth Factor
  • Immunity, Innate
  • Inflammation
  • Intestines
  • Lymphocytes
  • Tumor Necrosis Factor-alpha

Identity

PubMed Central ID

  • PMC8842850

Scopus Document Identifier

  • 85123930324

Digital Object Identifier (DOI)

  • 10.1007/978-1-4939-1212-4_18

PubMed ID

  • 35102343

Additional Document Info

volume

  • 23

issue

  • 2