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

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.

Basic information

Original name

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

Authors

BRABEC, Tomas (203 Czech Republic), Matouš VOBOŘIL (203 Czech Republic), Dagmar SCHIEROVA (203 Czech Republic), Evgeny VALTER (203 Czech Republic), Iva SPLICHALOVA (203 Czech Republic), Jan DOBEŠ (203 Czech Republic), Jiri BREZINA (203 Czech Republic), Martina DOBESOVA (203 Czech Republic), Aigerim AIDAROVA (203 Czech Republic), Martin JAKUBEC (203 Czech Republic), Jasper MANNING (203 Czech Republic), Richard BLUMBERG (203 Czech Republic), Ari WAISSMAN (203 Czech Republic), Michal KOLAR (203 Czech Republic), Jan KUBOVCIAK (203 Czech Republic), Dagmar SRUTKOVA (203 Czech Republic), Tomas HUDCOVIC (203 Czech Republic), Martin SCHWARZER (203 Czech Republic), Eva FRONKOVA (203 Czech Republic), Tereza PINKASOVÁ (203 Czech Republic, belonging to the institution), Petr JABANDŽIEV (203 Czech Republic, belonging to the institution) and Dominik FILIPP (203 Czech Republic, guarantor)

Edition

Mucosal Immunology, NEW YORK, ELSEVIER SCIENCE INC, 2023, 1933-0219

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30102 Immunology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 8.000 in 2022

RIV identification code

RIV/00216224:14110/23:00130512

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1016/j.mucimm.2023.01.005

UT WoS

001066088900001

Keywords in English

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

Abstract

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.

Citovat

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 and Dominik FILIPP. IL-17 driven induction of Paneth cell antimicrobial functions protects the host from microbiota dysbiosis and inflammation in the ileum. Mucosal Immunology. NEW YORK: ELSEVIER SCIENCE INC, 2023, vol. 16, No 4, p. 373-385. ISSN 1933-0219. Available from: https://dx.doi.org/10.1016/j.mucimm.2023.01.005.

@article{2271099,
   author = {Brabec, Tomas and Vobořil, Matouš and Schierova, Dagmar and Valter, Evgeny and Splichalova, Iva and Dobeš, Jan and Brezina, Jiri and Dobesova, Martina and Aidarova, Aigerim and Jakubec, Martin and Manning, Jasper and Blumberg, Richard and Waissman, Ari and Kolar, Michal and Kubovciak, Jan and Srutkova, Dagmar and Hudcovic, Tomas and Schwarzer, Martin and Fronkova, Eva and Pinkasová, Tereza and Jabandžiev, Petr and Filipp, Dominik},
   article_location = {NEW YORK},
   article_number = {4},
   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},
   language = {eng},
   issn = {1933-0219},
   journal = {Mucosal Immunology},
   title = {IL-17 driven induction of Paneth cell antimicrobial functions protects the host from microbiota dysbiosis and inflammation in the ileum},
   url = {https://www.sciencedirect.com/science/article/pii/S1933021923000053?via%3Dihub},
   volume = {16},
   year = {2023}
}

TY  - JOUR
ID  - 2271099
AU  - Brabec, Tomas - Vobořil, Matouš - Schierova, Dagmar - Valter, Evgeny - Splichalova, Iva - Dobeš, Jan - Brezina, Jiri - Dobesova, Martina - Aidarova, Aigerim - Jakubec, Martin - Manning, Jasper - Blumberg, Richard - Waissman, Ari - Kolar, Michal - Kubovciak, Jan - Srutkova, Dagmar - Hudcovic, Tomas - Schwarzer, Martin - Fronkova, Eva - Pinkasová, Tereza - Jabandžiev, Petr - Filipp, Dominik
PY  - 2023
TI  - IL-17 driven induction of Paneth cell antimicrobial functions protects the host from microbiota dysbiosis and inflammation in the ileum
JF  - Mucosal Immunology
VL  - 16
IS  - 4
SP  - 373-385
EP  - 373-385
PB  - ELSEVIER SCIENCE INC
SN  - 19330219
KW  - Paneth cells
KW  - IL-17 Signaling
KW  - Antimicrobial peptides
KW  - Crohn's disease
KW  - ileal microbiota
UR  - https://www.sciencedirect.com/science/article/pii/S1933021923000053?via%3Dihub
N2  - 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.
ER  -

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 and Dominik FILIPP. IL-17 driven induction of Paneth cell antimicrobial functions protects the host from microbiota dysbiosis and inflammation in the ileum. \textit{Mucosal Immunology}. NEW YORK: ELSEVIER SCIENCE INC, 2023, vol.~16, No~4, p.~373-385. ISSN~1933-0219. Available from: https://dx.doi.org/10.1016/j.mucimm.2023.01.005.

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