Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • 100th Anniversary of Insulin's Discovery (Jan 2021)
    • Hypoxia-inducible factors in disease pathophysiology and therapeutics (Oct 2020)
    • Latency in Infectious Disease (Jul 2020)
    • Immunotherapy in Hematological Cancers (Apr 2020)
    • Big Data's Future in Medicine (Feb 2020)
    • Mechanisms Underlying the Metabolic Syndrome (Oct 2019)
    • Reparative Immunology (Jul 2019)
    • View all review series ...
  • Viewpoint
  • Collections
    • Recently published
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • Recently published
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
Mucosal IL-10 and TGF-β play crucial roles in preventing LPS-driven, IFN-γ–mediated epithelial damage in human colon explants
Anne Jarry, … , Marc G. Denis, Christian L. Laboisse
Anne Jarry, … , Marc G. Denis, Christian L. Laboisse
Published February 7, 2008
Citation Information: J Clin Invest. 2008;118(3):1132-1142. https://doi.org/10.1172/JCI32140.
View: Text | PDF
Research Article Gastroenterology

Mucosal IL-10 and TGF-β play crucial roles in preventing LPS-driven, IFN-γ–mediated epithelial damage in human colon explants

  • Text
  • PDF
Abstract

IL-10 is an immunomodulatory cytokine that plays an obligate role in preventing spontaneous enterocolitis in mice. However, little is known about IL-10 function in the human intestinal mucosa. We showed here that IL-10 was constitutively expressed and secreted by the human normal colonic mucosa, including epithelial cells. Depletion of IL-10 in mucosal explants induced both downregulation of the IL-10–inducible, immunosuppressive gene BCL3 and upregulation of IFN-γ, TNF-α, and IL-17. Interestingly, TGF-β blockade also strongly induced IFN-γ production. In addition, the high levels of IFN-γ produced upon IL-10 depletion were responsible for surface epithelium damage and crypt loss, mainly by apoptosis. Polymyxin B, used as a scavenger of endogenous LPS, abolished both IFN-γ production and epithelial barrier disruption. Finally, adding a commensal bacteria strain to mucosa explant cultures depleted of both IL-10 and LPS reproduced the ability of endogenous LPS to induce IFN-γ secretion. These findings demonstrate that IL-10 ablation leads to an endogenous IFN-γ–mediated inflammatory response via LPS from commensal bacteria in the human colonic mucosa. We also found that both IL-10 and TGF-β play crucial roles in maintaining human colonic mucosa homeostasis.

Authors

Anne Jarry, Céline Bossard, Chantal Bou-Hanna, Damien Masson, Eric Espaze, Marc G. Denis, Christian L. Laboisse

×

Full Text PDF | Download (963.83 KB)

Follow JCI:
Copyright © 2021 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts