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IL-33 signalling in liver immune cells enhances drug-induced liver injury and inflammation

Abstract : The aim of this study was to investigate the contribution of IL-33/ST2 axis in the onset and progression of acute liver injury using a mice model of drug-induced liver injury (DILI). DILI was induced by overdose administration of acetaminophen (APAP) by oral gavage in wild-type BALB/c, ST2-deficient mice and in different bone marrow chimeras. Neutrophils were depleted by anti-Ly6G and macrophages with clodronate liposomes (CLL). Blood and liver were collected for biochemical, immunologic and genetic analyses. Mice were imaged by confocal intravital microscopy and liver non-parenchymal cells and hepatocytes were isolated for flow cytometry, genetic and immunofluorescence studies. Acetaminophen overdose caused a massive necrosis and accumulation of immune cells within the liver, concomitantly with IL-33 and chemokine release. Liver non-parenchymal cells were the major sensors for IL-33, and amongst them, neutrophils were the major players in amplification of the inflammatory response triggered by IL-33/ST2 signalling pathway. Blockage of IL-33/ST2 axis reduces APAP-mediated organ injury by dampening liver chemokine release and activation of resident and infiltrating liver non-parenchymal cells.
Keywords : DAMPs ST2 Liver necrosis
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https://hal-cnrs.archives-ouvertes.fr/hal-02126492
Contributor : Valérie Quesniaux <>
Submitted on : Saturday, May 11, 2019 - 6:04:45 PM
Last modification on : Tuesday, May 26, 2020 - 3:41:01 AM

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Maísa Mota Antunes, Alan Moreira Araújo, Ariane Barros Diniz, Rafaela Vaz Sousa Pereira, Débora Moreira Alvarenga, et al.. IL-33 signalling in liver immune cells enhances drug-induced liver injury and inflammation. Inflammation Research, Springer Verlag, 2018, 67 (1), pp.77-88. ⟨10.1007/s00011-017-1098-3⟩. ⟨hal-02126492⟩

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