Gut microbiota‐CRAMP axis shapes intestinal barrier function and immune responses in dietary gluten‐induced enteropathy

Zhengnan Ren; Li‐Long Pan; Yiwen Huang; Hongbing Chen; Yu Liu; He Liu; Xing Tu; Yanyan Liu; Binbin Li; Xiaoliang Dong; Xiaohua Pan; Hanfei Li; Yu V Fu; Birgitta Agerberth; Julien Diana; Jia Sun

doi:10.15252/emmm.202114059

EMBO Molecular Medicine (Aug 2021)

Gut microbiota‐CRAMP axis shapes intestinal barrier function and immune responses in dietary gluten‐induced enteropathy

Zhengnan Ren,
Li‐Long Pan,
Yiwen Huang,
Hongbing Chen,
Yu Liu,
He Liu,
Xing Tu,
Yanyan Liu,
Binbin Li,
Xiaoliang Dong,
Xiaohua Pan,
Hanfei Li,
Yu V Fu,
Birgitta Agerberth,
Julien Diana,
Jia Sun

Affiliations

Zhengnan Ren: State Key Laboratory of Food Science and Technology Jiangnan University Wuxi China
Li‐Long Pan: Wuxi Medical School Jiangnan University Wuxi China
Yiwen Huang: State Key Laboratory of Food Science and Technology Jiangnan University Wuxi China
Hongbing Chen: State Key Laboratory of Food Science and Technology Nanchang University Nanchang China
Yu Liu: Department of Endocrinology and Metabolism Sir Run Run Shaw Hospital Nanjing Medical University Nanjing China
He Liu: State Key Laboratory of Food Science and Technology Jiangnan University Wuxi China
Xing Tu: State Key Laboratory of Food Science and Technology Jiangnan University Wuxi China
Yanyan Liu: State Key Laboratory of Food Science and Technology Jiangnan University Wuxi China
Binbin Li: State Key Laboratory of Food Science and Technology Jiangnan University Wuxi China
Xiaoliang Dong: State Key Laboratory of Food Science and Technology Jiangnan University Wuxi China
Xiaohua Pan: State Key Laboratory of Food Science and Technology Jiangnan University Wuxi China
Hanfei Li: State Key Laboratory of Microbial Resources Institute of Microbiology Chinese Academy of Sciences Beijing China
Yu V Fu: State Key Laboratory of Microbial Resources Institute of Microbiology Chinese Academy of Sciences Beijing China
Birgitta Agerberth: Department of Laboratory Medicine Division of Clinical Microbiology Karolinska Institutet Karolinska University Hospital Huddinge Stockholm Sweden
Julien Diana: Institut Necker Enfants Malades (INEM) Institut National de la Santé et de la Recherche Médicale (INSERM) Paris France
Jia Sun: State Key Laboratory of Food Science and Technology Jiangnan University Wuxi China

DOI: https://doi.org/10.15252/emmm.202114059
Journal volume & issue: Vol. 13, no. 8
pp. n/a – n/a

Abstract

Read online

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.

Published in EMBO Molecular Medicine

ISSN: 1757-4676 (Print); 1757-4684 (Online)
Publisher: Springer Nature
Country of publisher: United Kingdom
LCC subjects: Medicine: Medicine (General); Science: Biology (General): Genetics
Website: https://www.embopress.org/journal/17574684

About the journal

Abstract

Keywords