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

Frontiers in Immunology

Immunology

Julian Heuberger¹  Tilman Breiderhoff²  Christian Hudert²  Philip Bufler²  Laura Kröhn²  Aline Azabdaftari³  Matthias Zilbauer⁴ 

[1] Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, Germany;Department of Pediatric Gastroenterology, Nephrology and Metabolic Diseases, Charité Universitätsmedizin Berlin, Berlin, Germany;Department of Pediatric Gastroenterology, Nephrology and Metabolic Diseases, Charité Universitätsmedizin Berlin, Berlin, Germany;Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany;Wellcome Trust–Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom;

关键词: innate immune response;    inflammatory bowel disease;    IL-37;    intestinal organoid;    intestinal barrier;    tight junctions;    cytokines;   

DOI  :  10.3389/fimmu.2023.1261666

 received in 2023-07-19, accepted in 2023-08-31,  发布年份 2023

来源: Frontiers

【 摘 要 】

Background and AimsIntestinal 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.MethodsMurine intestinal organoids were generated from IL-37tg and wildtype mice. Human ileal organoids were generated from healthy young donors.ResultsExpression 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.ConclusionsWe speculate that the anti-inflammatory activity of IL-37 in the intestine is mainly mediated by lamina propria immune cells protecting intestinal epithelial integrity.

【 授权许可】

Unknown   
Copyright © 2023 Kröhn, Azabdaftari, Heuberger, Hudert, Zilbauer, Breiderhoff and Bufler