Fibrogenesis in chronic murine colitis is independent of innate lymphoid cells

INTRODUCTION: Insight in the pathogenesis of intestinal fibrosis is an unmet medical need in inflammatory bowel diseases. Studies in murine models and human organ fibrosis point to a potential role of innate lymphoid cells (ILC) in chronic intestinal inflammation and fibrosis. MATERIALS AND METHODS: Dextran sodium sulfate (DSS) in drinking water was used to induce chronic colitis and remodeling in C57Bl/6 wild type (WT), RAG‐deficient, RAG(−/−) common γ chain deficient and anti‐CD90.2 monoclonal antibody treated RAG(−/−) mice. Inflammation was scored by macroscopic and histological examination and fibrosis was evaluated by hydroxyproline quantification and histology. RESULTS: In RAG(−/−) mice (which have a normal ILC population but no adaptive immunity), chronic intestinal inflammation and fibrosis developed similarly as in WT mice, with a relative increase in ILC2 during repeated DSS exposure. Chronic colitis could also be induced in the absence of ILC (RAG(−/−)γc(−/−) or anti‐CD90.2 treated RAG(−/−) mice) with no attenuation of fibrosis. Importantly, clinical recovery based on weight gain after stopping DSS exposure was impaired in ILC‐deficient or ILC‐depleted mice. CONCLUSION: These data argue against a profibrotic effect of ILC in chronic colitis, but rather suggest that ILC have a protective and recovery‐enhancing effect after repeated intestinal injury.