Inducible T-Cell Costimulator Mediates Lymphocyte/Macrophage Interactions During Liver Repair

The liver capacity to recover from acute liver injury is a critical factor in the development of acute liver failure (ALF) caused by viral infections, ischemia/reperfusion or drug toxicity. Liver healing requires the switching of pro-inflammatory monocyte-derived macrophages(MoMFs) to a reparative p...

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Autores principales:	Naresh Naik Ramavath, Laila Lavanya Gadipudi, Alessia Provera, Luca C. Gigliotti, Elena Boggio, Cristina Bozzola, Emanuele Albano, Umberto Dianzani, Salvatore Sutti
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	acute liver injury liver inflammation liver healing carbon tetrachloride poisoning macrophage phenotype Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/1518e1223ad74f0f999f958a4de6a36f
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spelling	oai:doaj.org-article:1518e1223ad74f0f999f958a4de6a36f2021-12-03T07:13:32ZInducible T-Cell Costimulator Mediates Lymphocyte/Macrophage Interactions During Liver Repair1664-322410.3389/fimmu.2021.786680https://doaj.org/article/1518e1223ad74f0f999f958a4de6a36f2021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.786680/fullhttps://doaj.org/toc/1664-3224The liver capacity to recover from acute liver injury is a critical factor in the development of acute liver failure (ALF) caused by viral infections, ischemia/reperfusion or drug toxicity. Liver healing requires the switching of pro-inflammatory monocyte-derived macrophages(MoMFs) to a reparative phenotype. However, the mechanisms involved are still incompletely characterized. In this study we investigated the contribution of T-lymphocyte/macrophage interaction through the co-stimulatory molecule Inducible T-cell co-stimulator (ICOS; CD278) and its ligand (ICOSL; CD275) in modulating liver repair. The role of ICOS/ICOSL dyad was investigated during the recovery from acute liver damage induced by a single dose of carbon tetrachloride (CCl4). Flow cytometry of non-parenchymal liver cells obtained from CCl4-treated wild-type mice revealed that the recovery from acute liver injury associated with a specific up-regulation of ICOS in CD8+ T-lymphocytes and with an increase in ICOSL expression involving CD11bhigh/F4-80+ hepatic MoMFs. Although ICOS deficiency did not influence the severity of liver damage and the evolution of inflammation, CCl4-treated ICOS knockout (ICOS-/-) mice showed delayed clearance of liver necrosis and increased mortality. These animals were also characterized by a significant reduction of hepatic reparative MoMFs due to an increased rate of cell apoptosis. An impaired liver healing and loss of reparative MoMFs was similarly evident in ICOSL-deficient mice or following CD8+ T-cells ablation in wild-type mice. The loss of reparative MoMFs was prevented by supplementing CCl4-treated ICOS-/- mice with recombinant ICOS (ICOS-Fc) which also stimulated full recovery from liver injury. These data demonstrated that CD8+ T-lymphocytes play a key role in supporting the survival of reparative MoMFs during liver healing trough ICOS/ICOSL-mediated signaling. These observations open the possibility of targeting ICOS/ICOSL dyad as a novel tool for promoting efficient healing following acute liver injury.Naresh Naik RamavathLaila Lavanya GadipudiAlessia ProveraLuca C. GigliottiElena BoggioCristina BozzolaEmanuele AlbanoUmberto DianzaniSalvatore SuttiFrontiers Media S.A.articleacute liver injuryliver inflammationliver healingcarbon tetrachloride poisoningmacrophage phenotypeImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	acute liver injury liver inflammation liver healing carbon tetrachloride poisoning macrophage phenotype Immunologic diseases. Allergy RC581-607
spellingShingle	acute liver injury liver inflammation liver healing carbon tetrachloride poisoning macrophage phenotype Immunologic diseases. Allergy RC581-607 Naresh Naik Ramavath Laila Lavanya Gadipudi Alessia Provera Luca C. Gigliotti Elena Boggio Cristina Bozzola Emanuele Albano Umberto Dianzani Salvatore Sutti Inducible T-Cell Costimulator Mediates Lymphocyte/Macrophage Interactions During Liver Repair
description	The liver capacity to recover from acute liver injury is a critical factor in the development of acute liver failure (ALF) caused by viral infections, ischemia/reperfusion or drug toxicity. Liver healing requires the switching of pro-inflammatory monocyte-derived macrophages(MoMFs) to a reparative phenotype. However, the mechanisms involved are still incompletely characterized. In this study we investigated the contribution of T-lymphocyte/macrophage interaction through the co-stimulatory molecule Inducible T-cell co-stimulator (ICOS; CD278) and its ligand (ICOSL; CD275) in modulating liver repair. The role of ICOS/ICOSL dyad was investigated during the recovery from acute liver damage induced by a single dose of carbon tetrachloride (CCl4). Flow cytometry of non-parenchymal liver cells obtained from CCl4-treated wild-type mice revealed that the recovery from acute liver injury associated with a specific up-regulation of ICOS in CD8+ T-lymphocytes and with an increase in ICOSL expression involving CD11bhigh/F4-80+ hepatic MoMFs. Although ICOS deficiency did not influence the severity of liver damage and the evolution of inflammation, CCl4-treated ICOS knockout (ICOS-/-) mice showed delayed clearance of liver necrosis and increased mortality. These animals were also characterized by a significant reduction of hepatic reparative MoMFs due to an increased rate of cell apoptosis. An impaired liver healing and loss of reparative MoMFs was similarly evident in ICOSL-deficient mice or following CD8+ T-cells ablation in wild-type mice. The loss of reparative MoMFs was prevented by supplementing CCl4-treated ICOS-/- mice with recombinant ICOS (ICOS-Fc) which also stimulated full recovery from liver injury. These data demonstrated that CD8+ T-lymphocytes play a key role in supporting the survival of reparative MoMFs during liver healing trough ICOS/ICOSL-mediated signaling. These observations open the possibility of targeting ICOS/ICOSL dyad as a novel tool for promoting efficient healing following acute liver injury.
format	article
author	Naresh Naik Ramavath Laila Lavanya Gadipudi Alessia Provera Luca C. Gigliotti Elena Boggio Cristina Bozzola Emanuele Albano Umberto Dianzani Salvatore Sutti
author_facet	Naresh Naik Ramavath Laila Lavanya Gadipudi Alessia Provera Luca C. Gigliotti Elena Boggio Cristina Bozzola Emanuele Albano Umberto Dianzani Salvatore Sutti
author_sort	Naresh Naik Ramavath
title	Inducible T-Cell Costimulator Mediates Lymphocyte/Macrophage Interactions During Liver Repair
title_short	Inducible T-Cell Costimulator Mediates Lymphocyte/Macrophage Interactions During Liver Repair
title_full	Inducible T-Cell Costimulator Mediates Lymphocyte/Macrophage Interactions During Liver Repair
title_fullStr	Inducible T-Cell Costimulator Mediates Lymphocyte/Macrophage Interactions During Liver Repair
title_full_unstemmed	Inducible T-Cell Costimulator Mediates Lymphocyte/Macrophage Interactions During Liver Repair
title_sort	inducible t-cell costimulator mediates lymphocyte/macrophage interactions during liver repair
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/1518e1223ad74f0f999f958a4de6a36f
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Inducible T-Cell Costimulator Mediates Lymphocyte/Macrophage Interactions During Liver Repair

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