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Updated: Sep 17, 2025

Analyzing Beneficial Effects of Nutritional Supplements on Intestinal Epithelial Barrier Functions During Experimental Colitis
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Elevated nitric oxide during colitis restrains GM-CSF production in ILC3 cells via suppressing an AhR-Cyp4f13-NF-κB

Xingyu Zhao1,2, Jun Li3, Yime Zhang1,4

  • 1Department of Immunology, School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology, Medicine Innovation Center for Fundamental Researches on Major Immunology-Related Diseases, Peking University, Beijing, China.

Nature Communications
|July 2, 2025
PubMed

Insights

Nitric oxide (NO) restrains inflammatory bowel disease (IBD) by regulating immune cells. Restoring NO binding to colonic ILC3s in IBD patients may reduce disease activity.

Area of Science:

  • Immunology
  • Gastroenterology
  • Molecular Biology

Background:

  • Inflammatory bowel disease (IBD) poses a significant clinical challenge.
  • The role of bioactive gases in IBD pathogenesis is not fully understood.

Purpose of the Study:

  • To investigate the role of nitric oxide (NO) and its related pathways in IBD.
  • To identify mechanisms by which NO regulates immune responses in the colon.

Main Methods:

  • Analysis of colonic Nos2 levels in IBD patients and colitis models.
  • Investigating the effect of Nos2 deficiency on colitis severity and GM-CSF production.
  • Examining the role of AhR, Cyp4f13, and NO in ILC3 function.
  • Utilizing a Cyp4f13 inhibitor (HET0016) to assess therapeutic potential.

Main Results:

  • Elevated colonic Nos2 levels were observed in IBD patients and colitis models.
  • Nos2 deficiency exacerbated colitis and increased GM-CSF production by ILC3s.
  • AhR promotes Cyp4f13 expression, enabling ILC3s to bind external NO, which restrains ROS generation and NF-κB activation, thereby reducing GM-CSF production.
  • HET0016 treatment ameliorated exacerbated colitis in Nos2-deficient mice.
  • IBD patients with increased NO binding to colonic ILC3s exhibited decreased disease activity.

Conclusions:

  • A novel regulatory mechanism involving NO, AhR, and Cyp4f13 restrains colitogenic GM-CSF production in ILC3s.
  • This pathway represents a potential therapeutic target for IBD.
  • Restoring NO binding to colonic ILC3s may be beneficial for IBD treatment.

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