Endogenous IL-33 Deficiency Exacerbates Liver Injury and Increases Hepatic Influx of Neutrophils in Acute Murine Viral Hepatitis. (4th May 2017)

• Record Type: Journal Article
• Authors: Carrière, Virginie; Arshad, Muhammad Imran; Le Seyec, Jacques; Lefevre, Benjamin; Farooq, Muhammad; Jan, Aurélien; Manuel, Christelle; Touami-Bernard, Laurence; Lucas-Clerc, Catherine; Genet, Valentine; Gascan, Hugues; Girard, Jean-Philippe; Chalmel, Frédéric; Lamontagne, Lucie; Piquet-Pellorce, Claire; Samson, Michel
• Other Names: Kleinjan Alex Academic Editor.
• Is Part Of: Mediators of inflammation. Volume 2017(2017)
• Publication Date: 2017-05-04
• Subjects: Inflammation -- Mediators -- Periodicals; Biological response modifiers -- Periodicals; Inflammation (Pathologie) -- Médiateurs; Immunomodulateurs; Biological response modifiers; Inflammation -- Mediators; Immunology; Autacoids; Immunologic Factors; Cell Adhesion Molecules; Cell Communication; Cytokines; Inflammation; Periodicals; Electronic journals; 616.0473
• DOI: 10.1155/2017/1359064
• Languages: English
• ISSNs: 0962-9351

Abstract

Abstract : 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, TNF α, 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 IFN γ was strongly induced in WT mice with less profound expression in IL-33 KO mice demonstrating that endogenous IL-33 regulated IFN γ expression during L2-MHV3 hepatitis. In conclusion, we demonstrated that endogenous IL-33 had multifaceted immunoregulatory effect during viral hepatitis via induction of IFN γ, survival effect on immune cells, and infiltration of neutrophils in the liver.