OP37 Fibrogenesis in chronic DSS colitis is driven by an innate lymphoid cell-independent innate immune response
B. Creyns1,2, J. Cremer1,2, G. De Hertogh3, L. Boon4, M. Ferrante2,5, S. Vermeire2,5, G. Van Assche2,5, J. Ceuppens1, C. Breynaert1,6, Allergy and Clinical Immunology Research Group
1Department of Microbiology, Immunology and Transplantation, Allergy and Clinical Immunology Research Group, KU Leuven, Leuven, Belgium, 2Department of Chronic Diseases, Metabolism and Ageing, Translational Research Center for Gastrointestinal Disorders TARGID, KU Leuven, Leuven, Belgium, 3Department of Imaging and Pathology, Translational Cell and Tissue Research, KU Leuven, Leuven, Belgium, 4Bioceros, Utrecht, The Netherlands, 5Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium, 6Department of General Internal Medicine, KU Leuven, University Hospitals Leuven, Leuven, Belgium
Background
Obtaining insights in the pathogenesis of intestinal fibrosis is a priority for improving outcomes in inflammatory bowel diseases (IBD). Studies in murine models and human organ fibrosis indicate a role for innate immunity pathways in fibrosis. The aim of this study was to dissect the role of innate lymphoid cells (ILC) in chronic intestinal inflammation and fibrosis.
Methods
A chronic 3-cycles dextran sulphate sodium (DSS) model was induced in wild-type (WT), recombinant activating gene (RAG)-deficient (lacking adaptive immunity), RAG−/− common γ-chain (ɣc)−/− (lacking ILC) and anti-CD90.2 treated (ILC depleted) C57Bl/6 RAG−/− mice. One cycle of DSS comprised 1 week of DSS administration followed by 2 weeks of recovery with normal drinking water. Colonic lamina propria cells were isolated and CD45+Lineage−CD127+CD90.2+ ILC, Ly6C+ monocytes and Ly6G+ neutrophils were identified after staining by flow cytometry. Inflammation and fibrosis were scored by macroscopic and HE and Martius Scarlet Blue staining and fibrosis was evaluated by hydroxyproline quantification. For analysis Kruskal–Wallis testing with multiple Dunn’s comparisons was performed.
Results
In RAG-1−/− mice chronic inflammation and fibrosis developed similarly as in WT mice, with elevated KLRG-1+ ILC2 (68.90 vs. 48.00% of ILC,
Conclusion
These data argue against a pro-fibrotic role of ILC in the induction of fibrosis in chronic DSS colitis, and suggest a protective and recovery-enhancing role of ILC after repeated intestinal injury.