| First Author | Brabec T | Year | 2023 |
| Journal | Mucosal Immunol | Volume | 16 |
| Issue | 4 | Pages | 373-385 |
| PubMed ID | 36739089 | Mgi Jnum | J:356782 |
| Mgi Id | MGI:7762874 | Doi | 10.1016/j.mucimm.2023.01.005 |
| Citation | Brabec T, et al. (2023) 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 |
| abstractText | 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. |
