IL-17-driven induction of Paneth cell antimicrobial functions protects the host from microbiota dysbiosis and inflammation in the ileum

0574413 - ÚMG 2024 RIV DE eng J - Článek v odborném periodiku
Brabec, Tomáš - Vobořil, Matouš - Schierová, Dagmar - Valter, Evgeny - Šplíchalová, Iva - Dobeš, J. - Březina, Jiří - Dobešová, Martina - Aidarova, Aigerim - Jakubec, Martin - Manning, Jasper - Blumberg, R.S. - Waisman, A. - Kolář, Michal - Kubovčiak, Jan - Šrůtková, Dagmar - Hudcovic, Tomáš - Schwarzer, Martin - Froňková, E. - Pinkasová, T. - Jabandžiev, P. - Filipp, Dominik
IL-17-driven induction of Paneth cell antimicrobial functions protects the host from microbiota dysbiosis and inflammation in the ileum.
Mucosal Immunology. Roč. 16, č. 4 (2023), s. 373-385. ISSN 1933-0219. E-ISSN 1935-3456
Grant CEP: GA ČR(CZ) GA17-25365S; GA ČR(CZ) GA19-08294S
Grant ostatní: European Molecular Biology Organization (EMBO)(CZ) EMBO Installation grant 2018
Institucionální podpora: RVO:68378050 ; RVO:67985904 ; RVO:61388971
Klíčová slova: Interleukin (IL)-17 * Paneth cells (PCs) * IL-17 receptor (IL-17R) * antimicrobial functions * ileum
Obor OECD: Immunology; Microbiology (UZFG-Y); Immunology (MBU-M)
Impakt faktor: 8, rok: 2022
Způsob publikování: Open access
https://www.sciencedirect.com/science/article/pii/S1933021923000053?via%3Dihub

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.
Trvalý link: https://hdl.handle.net/11104/0344744