IL-17-driven induction of Paneth cell antimicrobial functions protects the host from microbiota dysbiosis and inflammation in the ileum
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
Grant support
R01 DK088199
NIDDK NIH HHS - United States
PubMed
36739089
DOI
10.1016/j.mucimm.2023.01.005
PII: S1933-0219(23)00005-3
Knihovny.cz E-resources
- MeSH
- Antimicrobial Peptides MeSH
- Child MeSH
- Dysbiosis microbiology MeSH
- Ileitis * microbiology MeSH
- Ileum microbiology MeSH
- Interleukin-17 MeSH
- Humans MeSH
- Microbiota * MeSH
- Mice MeSH
- Paneth Cells pathology MeSH
- Receptors, Interleukin-17 * genetics MeSH
- Inflammation pathology MeSH
- Animals MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
- Names of Substances
- Antimicrobial Peptides MeSH
- Il17ra protein, mouse MeSH Browser
- Interleukin-17 MeSH
- Receptors, Interleukin-17 * MeSH
Interleukin (IL)-17 protects epithelial barriers by inducing the secretion of antimicrobial peptides. However, the effect of IL-17 on Paneth cells (PCs), the major producers of antimicrobial peptides in the small intestine, is unclear. Here, we show that the targeted ablation of the IL-17 receptor (IL-17R) in PCs disrupts their antimicrobial functions and decreases the frequency of ileal PCs. These changes become more pronounced after colonization with IL-17 inducing segmented filamentous bacteria. Mice with PCs that lack IL-17R show an increased inflammatory transcriptional profile in the ileum along with the severity of experimentally induced ileitis. These changes are associated with a decrease in the diversity of gut microbiota that induces a severe ileum pathology upon transfer to genetically susceptible mice, which can be prevented by the systemic administration of IL-17a/f in microbiota recipients. In an exploratory analysis of a small cohort of pediatric patients with Crohn's disease, we have found that a portion of these patients exhibits a low number of lysozyme-expressing ileal PCs and a high ileitis severity score, resembling the phenotype of mice with IL-17R-deficient PCs. Our study identifies IL-17R-dependent signaling in PCs as an important mechanism that maintains ileal homeostasis through the prevention of dysbiosis.
Brigham and Women's Hospital Gastroenterology Division Boston USA
Department of Cell Biology Faculty of Science Charles University Prague Czech Republic
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