Endogenous IL-33 Deficiency Exacerbates Liver Injury and Increases Hepatic Influx of Neutrophils in Acute Murine Viral Hepatitis

The alarmin IL-33 has been described to be upregulated in human and murine viral hepatitis. However, the role of endogenous IL-33 in viral hepatitis remains obscure. We aimed to decipher its function by infecting IL-33-deficient mice (IL-33 KO) and their wild-type (WT) littermates with pathogenic mo...

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Main Authors: Virginie Carrière, Muhammad Imran Arshad, Jacques Le Seyec, Benjamin Lefevre, Muhammad Farooq, Aurélien Jan, Christelle Manuel, Laurence Touami-Bernard, Catherine Lucas-Clerc, Valentine Genet, Hugues Gascan, Jean-Philippe Girard, Frédéric Chalmel, Lucie Lamontagne, Claire Piquet-Pellorce, Michel Samson
Format: Article
Language:English
Published: Wiley 2017-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2017/1359064
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author Virginie Carrière
Muhammad Imran Arshad
Jacques Le Seyec
Benjamin Lefevre
Muhammad Farooq
Aurélien Jan
Christelle Manuel
Laurence Touami-Bernard
Catherine Lucas-Clerc
Valentine Genet
Hugues Gascan
Jean-Philippe Girard
Frédéric Chalmel
Lucie Lamontagne
Claire Piquet-Pellorce
Michel Samson
author_facet Virginie Carrière
Muhammad Imran Arshad
Jacques Le Seyec
Benjamin Lefevre
Muhammad Farooq
Aurélien Jan
Christelle Manuel
Laurence Touami-Bernard
Catherine Lucas-Clerc
Valentine Genet
Hugues Gascan
Jean-Philippe Girard
Frédéric Chalmel
Lucie Lamontagne
Claire Piquet-Pellorce
Michel Samson
author_sort Virginie Carrière
collection DOAJ
description The alarmin IL-33 has been described to be upregulated in human and murine viral hepatitis. However, the role of endogenous IL-33 in viral hepatitis remains obscure. We aimed to decipher its function by infecting IL-33-deficient mice (IL-33 KO) and their wild-type (WT) littermates with pathogenic mouse hepatitis virus (L2-MHV3). The IL-33 KO mice were more sensitive to L2-MHV3 infection exhibiting higher levels of AST/ALT, higher tissue damage, significant weight loss, and earlier death. An increased depletion of B and T lymphocytes, NKT cells, dendritic cells, and macrophages was observed 48 h postinfection (PI) in IL-33 KO mice than that in WT mice. In contrast, a massive influx of neutrophils was observed in IL-33 KO mice at 48 h PI. A transcriptomic study of inflammatory and cell-signaling genes revealed the overexpression of IL-6, TNFα, and several chemokines involved in recruitment/activation of neutrophils (CXCL2, CXCL5, CCL2, and CCL6) at 72 h PI in IL-33 KO mice. However, the IFNγ was strongly induced in WT mice with less profound expression in IL-33 KO mice demonstrating that endogenous IL-33 regulated IFNγ expression during L2-MHV3 hepatitis. In conclusion, we demonstrated that endogenous IL-33 had multifaceted immunoregulatory effect during viral hepatitis via induction of IFNγ, survival effect on immune cells, and infiltration of neutrophils in the liver.
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spelling doaj-art-9fe8ff11580440da92d3947ef6e69c6e2025-02-03T05:50:15ZengWileyMediators of Inflammation0962-93511466-18612017-01-01201710.1155/2017/13590641359064Endogenous IL-33 Deficiency Exacerbates Liver Injury and Increases Hepatic Influx of Neutrophils in Acute Murine Viral HepatitisVirginie Carrière0Muhammad Imran Arshad1Jacques Le Seyec2Benjamin Lefevre3Muhammad Farooq4Aurélien Jan5Christelle Manuel6Laurence Touami-Bernard7Catherine Lucas-Clerc8Valentine Genet9Hugues Gascan10Jean-Philippe Girard11Frédéric Chalmel12Lucie Lamontagne13Claire Piquet-Pellorce14Michel Samson15Institut National de la Santé et de la Recherche Médicale (Inserm), U.1085, Institut de Recherche Santé Environnement et Travail (IRSET), 35043 Rennes, FranceInstitut National de la Santé et de la Recherche Médicale (Inserm), U.1085, Institut de Recherche Santé Environnement et Travail (IRSET), 35043 Rennes, FranceInstitut National de la Santé et de la Recherche Médicale (Inserm), U.1085, Institut de Recherche Santé Environnement et Travail (IRSET), 35043 Rennes, FranceInstitut National de la Santé et de la Recherche Médicale (Inserm), U.1085, Institut de Recherche Santé Environnement et Travail (IRSET), 35043 Rennes, FranceInstitut National de la Santé et de la Recherche Médicale (Inserm), U.1085, Institut de Recherche Santé Environnement et Travail (IRSET), 35043 Rennes, FranceInstitut National de la Santé et de la Recherche Médicale (Inserm), U.1085, Institut de Recherche Santé Environnement et Travail (IRSET), 35043 Rennes, FranceInstitut National de la Santé et de la Recherche Médicale (Inserm), U.1085, Institut de Recherche Santé Environnement et Travail (IRSET), 35043 Rennes, FranceUniversité de Rennes 1, 35043 Rennes, FranceUniversité de Rennes 1, 35043 Rennes, FranceInstitut National de la Santé et de la Recherche Médicale (Inserm), U.1085, Institut de Recherche Santé Environnement et Travail (IRSET), 35043 Rennes, FranceInstitut de Génétique et Développement de Rennes (IGDR), UMR 6290 CNRS, Université de Rennes 1, 35043 Rennes, FranceInstitut de Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique (IPBS-CNRS), Université de Toulouse, 31077 Toulouse, FranceInstitut National de la Santé et de la Recherche Médicale (Inserm), U.1085, Institut de Recherche Santé Environnement et Travail (IRSET), 35043 Rennes, FranceDépartement des Sciences Biologiques, Université du Québec à Montréal, Montréal, QC, CanadaInstitut National de la Santé et de la Recherche Médicale (Inserm), U.1085, Institut de Recherche Santé Environnement et Travail (IRSET), 35043 Rennes, FranceInstitut National de la Santé et de la Recherche Médicale (Inserm), U.1085, Institut de Recherche Santé Environnement et Travail (IRSET), 35043 Rennes, FranceThe alarmin IL-33 has been described to be upregulated in human and murine viral hepatitis. However, the role of endogenous IL-33 in viral hepatitis remains obscure. We aimed to decipher its function by infecting IL-33-deficient mice (IL-33 KO) and their wild-type (WT) littermates with pathogenic mouse hepatitis virus (L2-MHV3). The IL-33 KO mice were more sensitive to L2-MHV3 infection exhibiting higher levels of AST/ALT, higher tissue damage, significant weight loss, and earlier death. An increased depletion of B and T lymphocytes, NKT cells, dendritic cells, and macrophages was observed 48 h postinfection (PI) in IL-33 KO mice than that in WT mice. In contrast, a massive influx of neutrophils was observed in IL-33 KO mice at 48 h PI. A transcriptomic study of inflammatory and cell-signaling genes revealed the overexpression of IL-6, TNFα, and several chemokines involved in recruitment/activation of neutrophils (CXCL2, CXCL5, CCL2, and CCL6) at 72 h PI in IL-33 KO mice. However, the IFNγ was strongly induced in WT mice with less profound expression in IL-33 KO mice demonstrating that endogenous IL-33 regulated IFNγ expression during L2-MHV3 hepatitis. In conclusion, we demonstrated that endogenous IL-33 had multifaceted immunoregulatory effect during viral hepatitis via induction of IFNγ, survival effect on immune cells, and infiltration of neutrophils in the liver.http://dx.doi.org/10.1155/2017/1359064
spellingShingle Virginie Carrière
Muhammad Imran Arshad
Jacques Le Seyec
Benjamin Lefevre
Muhammad Farooq
Aurélien Jan
Christelle Manuel
Laurence Touami-Bernard
Catherine Lucas-Clerc
Valentine Genet
Hugues Gascan
Jean-Philippe Girard
Frédéric Chalmel
Lucie Lamontagne
Claire Piquet-Pellorce
Michel Samson
Endogenous IL-33 Deficiency Exacerbates Liver Injury and Increases Hepatic Influx of Neutrophils in Acute Murine Viral Hepatitis
Mediators of Inflammation
title Endogenous IL-33 Deficiency Exacerbates Liver Injury and Increases Hepatic Influx of Neutrophils in Acute Murine Viral Hepatitis
title_full Endogenous IL-33 Deficiency Exacerbates Liver Injury and Increases Hepatic Influx of Neutrophils in Acute Murine Viral Hepatitis
title_fullStr Endogenous IL-33 Deficiency Exacerbates Liver Injury and Increases Hepatic Influx of Neutrophils in Acute Murine Viral Hepatitis
title_full_unstemmed Endogenous IL-33 Deficiency Exacerbates Liver Injury and Increases Hepatic Influx of Neutrophils in Acute Murine Viral Hepatitis
title_short Endogenous IL-33 Deficiency Exacerbates Liver Injury and Increases Hepatic Influx of Neutrophils in Acute Murine Viral Hepatitis
title_sort endogenous il 33 deficiency exacerbates liver injury and increases hepatic influx of neutrophils in acute murine viral hepatitis
url http://dx.doi.org/10.1155/2017/1359064
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