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Interleukin-27 Regulates the Function of the Gastrointestinal Epithelial Barrier in a Human Tissue-Derived Organoid Model

  1. Author:
    Brice, Daniel P [ORCID]
    Murray, Graeme I
    Wilson, Heather M [ORCID]
    Porter, Ross J [ORCID]
    Berry, Susan
    Durum,Scott
    McLean, Mairi H [ORCID]

  2. Author Address

    School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen AB25 2ZD, UK., Centre for Inflammation Research, Queens Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK., Cytokines and Immunity Section, Laboratory of Cancer Immunometabolism, National Cancer Institute (NCI), National Institute of Health (NIH), Frederick, MD 21702, USA., Division of Molecular & Clinical Medicine, School of Medicine, University of Dundee, Dundee DD1 9SY, UK.,
    1. Year: 2022
    2. Date: Mar 11
    3. Epub Date: 2022 03 11
  2. Journal: Biology
    1. 11
    2. 3
  4. Type of Article: Article
  5. Article Number: 427
  1. Abstract:

    A treatment with direct healing effects on the gastrointestinal epithelial barrier is desirable for inflammatory bowel disease (IBD). Interleukin-27 (IL-27) is an immunoregulatory cytokine, and oral delivery is an effective treatment in murine models of IBD. We aimed to define IL-27 effects on the human gastrointestinal epithelial barrier. We characterised gene and protein expression of permeability mediators in a human colon-derived organoid model. Functional permeability was determined in an organoid-derived 2D monolayer by transepithelial electrical resistance. IL-27 effects on epithelial innate immune responses were assessed through expression of cytokines, anti-microbial peptides and MUC genes. IL-27 effects on wound healing and proliferation were determined in human colon epithelial cell lines. IL-27 led to restoration of permeability regulation following inflammatory cytokine insult (p = 0.001), associated with differential expression of tight junction mediators with decrease in claudin 2 (p = 0.024) and increase in claudin 4 (p < 0.001), E-cadherin (p < 0.001) and zona occludens (p = 0.0014). IL-27 evoked differential gene expression of epithelial-derived innate immune responses (reduced IL1B and IL18, and increased IL33, HBD1, MUC1 and MUC2; p < 0.012). IL-27 induced epithelial barrier wound healing through restitution (p < 0.001), and increased proliferation (p < 0.001) following injury. Overall, IL-27 provokes mucosal healing of the human gastrointestinal epithelial barrier.

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External Sources

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  2. DOI: 10.3390/biology11030427
  3. PMID: 35336801
  4. PMCID: PMC8945023
  5. PII : biology11030427

Library Notes

  1. Fiscal Year: FY2021-2022
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