Publication details
IL-17 driven induction of Paneth cell antimicrobial functions protects the host from microbiota dysbiosis and inflammation in the ileum
| Authors | |
|---|---|
| Year of publication | 2023 |
| Type | Article in Periodical |
| Magazine / Source | Mucosal Immunology |
| MU Faculty or unit | |
| Citation | |
| web | https://www.sciencedirect.com/science/article/pii/S1933021923000053?via%3Dihub |
| Doi | http://dx.doi.org/10.1016/j.mucimm.2023.01.005 |
| Keywords | Paneth cells; IL-17 Signaling; Antimicrobial peptides; Crohn's disease; ileal microbiota |
| Description | IL-17 protects epithelial barriers by inducing the secretion of antimicrobial peptides (AMPs). However, the effect of IL-17 on Paneth cells (PCs), the major producers of AMPs in the small intestine, is unclear. Here, we show that 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 (SFB). 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 exhibit 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. |