Epithelial dysfunction is prevented by IL-22 treatment in a Citrobacter rodentium-induced colitis model that shares similarities with inflammatory bowel disease

Autor: Qifan Zhu, Daniel Korenfeld, Abel Suarez-Fueyo, Sean Graham, Liang Jin, Shivesh Punit, Rachael Duffy, Munish Puri, Andrew Caruso, Chenqi Hu, Yu Tian, Bradford L. McRae, Raj Kamath, Lucy Phillips, Annette J. Schwartz-Sterman, Susan Westmoreland, Xiaohong Cao, Marc C. Levesque, Yingtao Bi, Jesus Paez-Cortez, Radhika Goenka
Rok vydání: 2021
Předmět:
Zdroj: Mucosal immunology. 15(6)
ISSN: 1935-3456
Popis: Inflammatory bowel disease (IBD) is characterized by a dysregulated intestinal epithelial barrier leading to breach of barrier immunity. Here we identified similar protein expression changes between IBD and Citrobacter rodentium-infected FVB mice with respect to dysregulation of solute transporters as well as components critical for intestinal barrier integrity. We attribute the disease associated changes in the model to the emergence of undifferentiated intermediate intestinal epithelial cells. Prophylactic treatment with IL-22.Fc in C. rodentium-infected FVB mice reduced disease severity and rescued the mice from lethality. Multi-omics and solute analyses revealed that IL-22.Fc treatment prevented disease-associated changes including disruption of the solute transporter machinery and restored proper physiological functions of the intestine, respectively. Taken together, we established the disease relevance of the C. rodentium-induced colitis model to IBD, demonstrated the protective role of IL-22 in amelioration of epithelial dysfunction and elucidated the molecular mechanisms with IL-22's effect on intestinal epithelial cells.
Databáze: OpenAIRE