AUTHOR=Kröhn Laura , Azabdaftari Aline , Heuberger Julian , Hudert Christian , Zilbauer Matthias , Breiderhoff Tilman , Bufler Philip 

TITLE=Modulation of intestinal IL-37 expression and its impact on the epithelial innate immune response and barrier integrity

JOURNAL=Frontiers in Immunology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1261666

DOI=10.3389/fimmu.2023.1261666

ISSN=1664-3224

ABSTRACT=Intestinal epithelial cells separate the luminal flora from lamina propria immune cells and regulate innate immune responses of the gut. An imbalance of the mucosal immune response and a 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. Expression of transgene IL-37 or recombinant IL-37Transgene IL-37 in intestinal organoids 2 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 and decreased expression upon IFN-gamma stimulation. Transgene IL-37 expression did not rescue TNFα-induced changes in morphology as well as ZO-1, occludin, claudin-2 and E-cadherin expression pattern of murine jejunal organoids. 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.