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Updated: Sep 10, 2025
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Intravital Imaging of Intraepithelial Lymphocytes in Murine Small Intestine
Published on: June 24, 2019
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New Perspectives on Paracrine IL-18 Signaling in the Intestinal Epithelium.
Nathaniel J Winsor1,2, Adrienne Ranger2, Ojas Singh2
1Department of Immunology, University of Toronto, Toronto, Canada.
DNA and Cell Biology
|August 20, 2025
Summary
Interleukin-18 (IL-18) has a newly discovered intrinsic signaling pathway within intestinal epithelial cells (IECs), impacting gut health and disease. This pathway involves specific IEC populations and offers new insights into intestinal inflammation.
Area of Science:
- Immunology
- Gastroenterology
- Cell Biology
Background:
- Interleukin-18 (IL-18) is a cytokine crucial for inflammatory responses, primarily known for its epithelial-out signaling from intestinal epithelial cells (IECs).
- Upon intestinal barrier breach, inflammasome activation leads to IL-18 maturation and release, activating immune cells via IL-18 receptor 1 (IL18R1).
Discussion:
- A novel epithelial-intrinsic IL-18 signaling pathway has been identified in the murine small intestine.
- This pathway involves IL18R1-expressing enterochromaffin cells and revival stem cells (revSCs) within the intestinal crypt during recovery.
- The discovery challenges the traditional view of IL-18 solely as an extracellular mediator.
Key Insights:
- IL-18 acts intrinsically within specific IEC populations, not just extracellularly.
- Enterochromaffin cells and revSCs are identified as key players in this intrinsic pathway.
- This finding provides a new perspective on the regulation of intestinal homeostasis and inflammation.
Outlook:
- Further research is needed to elucidate the precise mechanisms and physiological relevance of this intrinsic IL-18 pathway.
- Understanding this pathway could reveal new therapeutic targets for inflammatory and other intestinal diseases.
- Investigating the role of intrinsic IL-18 signaling in human intestinal conditions is a critical next step.
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