J 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

EID Scopus

Klíčová slova anglicky

Paneth cells; IL-17 Signaling; Antimicrobial peptides; Crohn's disease; ileal microbiota

Štítky

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.