IL-22 Prevents Epithelial Dysfunction During Citrobacter rodentium-induced Infectious Colitis

IBD is a complex autoimmune disease characterized by dysregulated interactions between host immune responses and microbiome at the intestinal epithelium interface. Here we identified shared protein alterations in intestinal epithelial differentiation and function between IBD and Citrobacter rodentium infected FVB mice. We discovered that prophylactic treatment with the mucosal healing therapy IL-22.Fc in the infected FVB mice reduced disease severity and rescued the mice from lethality. Notably, we observed an emergence of intermediate undifferentiated intestinal epithelial cells upon infection, with disrupted expression of the solute transporter machinery as well as components critical for intestinal barrier integrity. Multi-omics analyses revealed that with IL-22.Fc treatment several disease associated changes were prevented (including disruption of the solute transporter machinery), and proper physiological homeostatic functions of the intestine was restored. Taken together, we unveiled the disease relevance of the C. rodentium induced colitis model to IBD and demonstrated the protective role of the mucosal healing therapy IL-22.Fc in ameliorating the epithelial dysfunction.