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Injections of Lipopolysaccharide into Mice to Mimic Entrance of Microbial-derived Products After Intestinal Barrier Breach
Published on: May 2, 2018
Gut microbiota-CRAMP axis shapes intestinal barrier function and immune responses in dietary gluten-induced
Zhengnan Ren1,2, Li-Long Pan3, Yiwen Huang1,2
1State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China.
Abstract:
In the gut, cathelicidin-related antimicrobial peptide (CRAMP) has been largely described for its anti-infective activities. With an increasing recognition of its immune regulatory effects in extra-intestinal diseases, the role of CRAMP in gluten-induced small intestinal enteropathy celiac disease remains unknown. This study aimed to investigate the unexplored role of CRAMP in celiac disease. By applying a mouse model of gluten-induced enteropathy (GIE) recapitulating small intestinal enteropathy of celiac disease, we observed defective CRAMP production in duodenal epithelium during GIE. CRAMP-deficient mice were susceptible to the development of GIE. Exogenous CRAMP corrected gliadin-triggered epithelial dysfunction and promoted regulatory immune responses at the intestinal mucosa. Additionally, GIE-associated gut dysbiosis with enriched Pseudomonas aeruginosa and production of the protease LasB contributed to defective intestinal CRAMP production. These results highlight microbiota-CRAMP axis in the modulation of barrier function and immune responses in GIE. Hence, modulating CRAMP may represent a therapeutic strategy for celiac disease.
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