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

Daniel P Brice; Graeme I. Murray; Heather M. Wilson; Ross J. Porter; Susan Berry; Scott K. Durum; Mairi H. McLean

doi:10.3390/biology11030427

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

Daniel P Brice, Graeme I. Murray, Heather M. Wilson, Ross J. Porter, Susan Berry, Scott K. Durum, Mairi H. McLean^* (Corresponding Author)

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

4 Downloads (Pure)

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
Article number	427
Number of pages	16
Journal	Biology
Volume	11
Issue number	3
Early online date	11 Mar 2022
DOIs	https://doi.org/10.3390/biology11030427
Publication status	Published - 11 Mar 2022

Bibliographical note

Funding: This research was funded by CICRA (CICRA: better lives for children with crohns and colitis. Available online: https://www.cicra.org (last accessed on 23 January 2022); Ph.D. studentship to DBP) and an NHS Grampian Endowment project grant.
Acknowledgments: We wish to acknowledge the Grampian Tissue Biorepository for assistance in tissue preparation. Organoids were stored at −80 ◦C at the University of Aberdeen. Graphical abstract was created using Biorender with a licence for use in publication (agreement number AD22YOD1N6). DBP now at Lydia Becker Institute of Immunology and Inflammation and Wellcome Centre for Cell-Matrix Research, University of Manchester, UK

Keywords

IBD
colitis
cytokine
interleukin-27
epithelium
organoid
gastrointestinal
permeability

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.3390/biology11030427Licence: CC BY

Brice_etal_B_Interleukin-27_Regulates_The_VoR
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Final published version, 1.48 MBLicence: CC BY

Cite this

@article{f8386a1ae4194e52b6e21360da8a4b6f,

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

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.",

keywords = "IBD, colitis, cytokine, interleukin-27, epithelium, organoid, gastrointestinal, permeability",

author = "Brice, {Daniel P} and Murray, {Graeme I.} and Wilson, {Heather M.} and Porter, {Ross J.} and Susan Berry and Durum, {Scott K.} and McLean, {Mairi H.}",

note = "Funding: This research was funded by CICRA (CICRA: better lives for children with crohns and colitis. Available online: https://www.cicra.org (last accessed on 23 January 2022); Ph.D. studentship to DBP) and an NHS Grampian Endowment project grant. Acknowledgments: We wish to acknowledge the Grampian Tissue Biorepository for assistance in tissue preparation. Organoids were stored at −80 ◦C at the University of Aberdeen. Graphical abstract was created using Biorender with a licence for use in publication (agreement number AD22YOD1N6). DBP now at Lydia Becker Institute of Immunology and Inflammation and Wellcome Centre for Cell-Matrix Research, University of Manchester, UK",

year = "2022",

month = mar,

day = "11",

doi = "10.3390/biology11030427",

language = "English",

volume = "11",

journal = "Biology",

issn = "2079-7737",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "3",

}

TY - JOUR

T1 - Interleukin-27 Regulates the Function of the Gastrointestinal Epithelial Barrier in a Human Tissue-Derived Organoid Model

AU - Brice, Daniel P

AU - Murray, Graeme I.

AU - Wilson, Heather M.

AU - Porter, Ross J.

AU - Berry, Susan

AU - Durum, Scott K.

AU - McLean, Mairi H.

N1 - Funding: This research was funded by CICRA (CICRA: better lives for children with crohns and colitis. Available online: https://www.cicra.org (last accessed on 23 January 2022); Ph.D. studentship to DBP) and an NHS Grampian Endowment project grant. Acknowledgments: We wish to acknowledge the Grampian Tissue Biorepository for assistance in tissue preparation. Organoids were stored at −80 ◦C at the University of Aberdeen. Graphical abstract was created using Biorender with a licence for use in publication (agreement number AD22YOD1N6). DBP now at Lydia Becker Institute of Immunology and Inflammation and Wellcome Centre for Cell-Matrix Research, University of Manchester, UK

PY - 2022/3/11

Y1 - 2022/3/11

N2 - 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.

AB - 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.

KW - IBD

KW - colitis

KW - cytokine

KW - interleukin-27

KW - epithelium

KW - organoid

KW - gastrointestinal

KW - permeability

U2 - 10.3390/biology11030427

DO - 10.3390/biology11030427

M3 - Article

SN - 2079-7737

VL - 11

JO - Biology

JF - Biology

IS - 3

M1 - 427

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

Access to Document

Fingerprint

Cite this