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.
Original language | English |
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Article number | 427 |
Number of pages | 16 |
Journal | Biology |
Volume | 11 |
Issue number | 3 |
DOIs | |
Publication status | Published - 11 Mar 2022 |
Keywords
- IBD
- colitis
- cytokine
- interleukin-27
- epithelium
- organoid
- gastrointestinal
- permeability
- Cytokine
- Organoid
- Permeability
- Epithelium
- Gastrointestinal
- Interleukin-27
- Colitis
ASJC Scopus subject areas
- General Agricultural and Biological Sciences
- General Biochemistry,Genetics and Molecular Biology
- General Immunology and Microbiology