Related Experiment Video
Updated: Oct 5, 2025

Co-Culture of Murine Small Intestine Epithelial Organoids with Innate Lymphoid Cells
Published on: March 23, 2022
Group 3 innate lymphoid cells produce the growth factor HB-EGF to protect the intestine from TNF-mediated
Lei Zhou1,2,3, Wenqing Zhou4,5,6, Ann M Joseph4,5,6
1Joan and Sanford I. Weill Department of Medicine, Division of Gastroenterology, Weill Cornell Medicine, New York, NY, USA. lez2004@med.cornell.edu.
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.
Related Concept Videos
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
Renewal of Intestinal Stem Cells
Lymphoid Cells and Tissues
Lymphoid cells consist of various types of immune system cells. These include B and T lymphocytes, which are responsible for producing antibodies and killing infected cells, respectively. Dendritic cells act as messengers between the innate and adaptive...
Role Of Notch Signalling In Intestinal Stem Cell Renewal
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Histology of the Small Intestine
The intestinal lining features transverse folds called circular folds, each housing fingerlike projections known as intestinal villi. These villi are covered by a layer of simple columnar epithelium, also referred to as...

