2023
IL-17 driven induction of Paneth cell antimicrobial functions protects the host from microbiota dysbiosis and inflammation in the ileum
BRABEC, Tomas; Matouš VOBOŘIL; Dagmar SCHIEROVA; Evgeny VALTER; Iva SPLICHALOVA et al.Základní údaje
Originální název
IL-17 driven induction of Paneth cell antimicrobial functions protects the host from microbiota dysbiosis and inflammation in the ileum
Autoři
BRABEC, Tomas; Matouš VOBOŘIL; Dagmar SCHIEROVA; Evgeny VALTER; Iva SPLICHALOVA; Jan DOBEŠ; Jiri BREZINA; Martina DOBESOVA; Aigerim AIDAROVA; Martin JAKUBEC; Jasper MANNING; Richard BLUMBERG; Ari WAISSMAN; Michal KOLAR; Jan KUBOVCIAK; Dagmar SRUTKOVA; Tomas HUDCOVIC; Martin SCHWARZER; Eva FRONKOVA; Tereza PINKASOVÁ; Petr JABANDŽIEV a Dominik FILIPP
Vydání
Mucosal Immunology, NEW YORK, ELSEVIER SCIENCE INC, 2023, 1933-0219
Další údaje
Jazyk
angličtina
Typ výsledku
Článek v odborném periodiku
Obor
30102 Immunology
Stát vydavatele
Spojené státy
Utajení
není předmětem státního či obchodního tajemství
Odkazy
Impakt faktor
Impact factor: 8.100
Označené pro přenos do RIV
Ano
Kód RIV
RIV/00216224:14110/23:00130512
Organizační jednotka
Lékařská fakulta
UT WoS
EID Scopus
Klíčová slova anglicky
Paneth cells; IL-17 Signaling; Antimicrobial peptides; Crohn's disease; ileal microbiota
Příznaky
Mezinárodní význam, Recenzováno
Změněno: 26. 1. 2024 08:02, Mgr. Tereza Miškechová
Anotace
V originále
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.