IL-17-driven induction of Paneth cell antimicrobial functions protects the host from microbiota dysbiosis and inflammation in the ileum.
Mucosal Immunol
; 16(4): 373-385, 2023 08.
Article
in En
| MEDLINE
| ID: mdl-36739089
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Receptors, Interleukin-17
/
Microbiota
/
Ileitis
Type of study:
Prognostic_studies
Limits:
Animals
/
Child
/
Humans
Language:
En
Journal:
Mucosal Immunol
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2023
Document type:
Article
Affiliation country:
Czech Republic