dc.contributor.author
Kröhn, Laura
dc.contributor.author
Azabdaftari, Aline
dc.contributor.author
Heuberger, Julian
dc.contributor.author
Hudert, Christian
dc.contributor.author
Zilbauer, Matthias
dc.contributor.author
Breiderhoff, Tilman
dc.contributor.author
Bufler, Philip
dc.date.accessioned
2024-06-03T12:23:47Z
dc.date.available
2024-06-03T12:23:47Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/43738
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-43453
dc.description.abstract
Background and Aims: Intestinal epithelial cells separate the luminal flora from lamina propria immune cells and regulate innate immune responses in the gut. An imbalance of the mucosal immune response and disrupted intestinal barrier integrity contribute to the evolution of inflammatory bowel diseases. Interleukin (IL)-37 has broad anti- inflammatory activity and is expressed by the human intestinal epithelium. Mice ectopically expressing human IL-37 show reduced epithelial damage and inflammation after DSS-induced colitis. Here, we investigated the impact of IL-37 on the innate immune response and tight junction protein expression of mouse intestinal organoids and the modulation of IL37 expression in human intestinal organoids.
Methods: Murine intestinal organoids were generated from IL-37tg and wildtype mice. Human ileal organoids were generated from healthy young donors.
Results: Expression of transgene IL-37 or recombinant IL-37 protein did not significantly reduce overall proinflammatory cytokine mRNA expression in murine intestinal organoids. However, higher IL37 expression correlated with a reduced proinflammatory cytokine response in murine colonic organoids. IL37 mRNA expression in human ileal organoids was modulated by proinflammatory cytokines showing an increased expression upon TNF-α-stimulation and decreased expression upon IFN-gamma stimulation. Transgene IL-37 expression did not rescue TNF-α-induced changes in morphology as well as ZO-1, occludin, claudin-2, and E-cadherin expression patterns of murine jejunal organoids.
Conclusions: We speculate that the anti-inflammatory activity of IL-37 in the intestine is mainly mediated by lamina propria immune cells protecting intestinal epithelial integrity.
en
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
innate immune response
en
dc.subject
inflammatory bowel disease
en
dc.subject
intestinal organoid
en
dc.subject
intestinal barrier
en
dc.subject
tight junctions
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
Modulation of intestinal IL-37 expression and its impact on the epithelial innate immune response and barrier integrity
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
1261666
dcterms.bibliographicCitation.doi
10.3389/fimmu.2023.1261666
dcterms.bibliographicCitation.journaltitle
Frontiers in Immunology
dcterms.bibliographicCitation.originalpublishername
Frontiers Media SA
dcterms.bibliographicCitation.volume
14
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
37799712
dcterms.isPartOf.eissn
1664-3224