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

Maísa Mota Antunes Alan Moreira Araújo Ariane Barros Diniz Rafaela Vaz Sousa Pereira Débora Moreira Alvarenga Bruna Araújo Araújo Renata Monti Rocha Maria Alice Freitas Lopes Sarah Cozzer Marchesi Brenda Naemi Nakagaki Pedro Elias Marques 1 Bernhard Ryffel 2 Valerie Quesniaux 2 Rodrigo Guabiraba Brito José Carlos Alves Filho Denise Carmona Cara Rafael Machado Rezende Gustavo Batista Menezes 3
1 mmunopharmacology, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas
2 INEM - Immunologie et Neurogénétique Expérimentales et Moléculaires
3 Laboratório de Imunobiofotônica, Departamento de Morfologia
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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Journal articles
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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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