CD5L is a pleiotropic player in liver fibrosis controlling damage, fibrosis and immune cell contentResearch in context
Background: Chronic hepatic inflammation leads to liver fibrosis, which may progress to cirrhosis, a condition with high morbidity. Our aim was to assess the as yet unknown role of innate immunity protein CD5L in liver fibrosis. Methods: CD5L was measured by ELISA in plasma samples from cirrhotic (n...
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Elsevier
2019-05-01
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Series: | EBioMedicine |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396419302919 |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Cristina Bárcena Gemma Aran Luís Perea Lucía Sanjurjo Érica Téllez Anna Oncins Helena Masnou Isabel Serra Mónica García-Gallo Leonor Kremer Margarita Sala Carolina Armengol Pau Sancho-Bru Maria-Rosa Sarrias |
spellingShingle |
Cristina Bárcena Gemma Aran Luís Perea Lucía Sanjurjo Érica Téllez Anna Oncins Helena Masnou Isabel Serra Mónica García-Gallo Leonor Kremer Margarita Sala Carolina Armengol Pau Sancho-Bru Maria-Rosa Sarrias CD5L is a pleiotropic player in liver fibrosis controlling damage, fibrosis and immune cell contentResearch in context EBioMedicine |
author_facet |
Cristina Bárcena Gemma Aran Luís Perea Lucía Sanjurjo Érica Téllez Anna Oncins Helena Masnou Isabel Serra Mónica García-Gallo Leonor Kremer Margarita Sala Carolina Armengol Pau Sancho-Bru Maria-Rosa Sarrias |
author_sort |
Cristina Bárcena |
title |
CD5L is a pleiotropic player in liver fibrosis controlling damage, fibrosis and immune cell contentResearch in context |
title_short |
CD5L is a pleiotropic player in liver fibrosis controlling damage, fibrosis and immune cell contentResearch in context |
title_full |
CD5L is a pleiotropic player in liver fibrosis controlling damage, fibrosis and immune cell contentResearch in context |
title_fullStr |
CD5L is a pleiotropic player in liver fibrosis controlling damage, fibrosis and immune cell contentResearch in context |
title_full_unstemmed |
CD5L is a pleiotropic player in liver fibrosis controlling damage, fibrosis and immune cell contentResearch in context |
title_sort |
cd5l is a pleiotropic player in liver fibrosis controlling damage, fibrosis and immune cell contentresearch in context |
publisher |
Elsevier |
series |
EBioMedicine |
issn |
2352-3964 |
publishDate |
2019-05-01 |
description |
Background: Chronic hepatic inflammation leads to liver fibrosis, which may progress to cirrhosis, a condition with high morbidity. Our aim was to assess the as yet unknown role of innate immunity protein CD5L in liver fibrosis. Methods: CD5L was measured by ELISA in plasma samples from cirrhotic (n = 63) and hepatitis (n = 39) patients, and healthy controls (n = 7), by immunohistochemistry in cirrhotic tissue (n = 12), and by quantitative RT-PCR in mouse liver cell subsets isolated by cell sorting. Recombinant CD5L (rCD5L) was administered into a murine model of CCl4-induced fibrosis, and damage, fibrosis and hepatic immune cell infiltration, including the LyC6hi (pro-fibrotic)-LyC6low (pro-resolutive) monocyte ratio were determined. Moreover, rCD5L was added into primary human hepatic stellate cells to study transforming growth factor β (TGFβ) activation responses. Findings: Cirrhotic patients showed elevated plasma CD5L concentrations as compared to patients with hepatitis and healthy controls (Mann-Whitney test p < 0·0001). Moreover, plasma CD5L correlated with disease progression, FIB4 fibrosis score (r:0·25, p < 0·0001) and tissue expression (r = 0·649; p = 0·022). Accordingly, CCl4-induced damage increased CD5L levels in total liver, particularly in hepatocytes and macrophages. rCD5L administration attenuated CCl4-induced injury and fibrosis as determined by reduced serum transaminase and collagen content. Moreover, rCD5L inhibited immune cell infiltration and promoted a phenotypic shift in monocytes from LyC6hi to LyC6low. Interestingly, rCD5L also had a direct effect on primary human hepatic stellate cells promoting SMAD7 expression, thus repressing TGFβ signalling. Interpretation: Our study identifies CD5L as a key pleiotropic inhibitor of chronic liver injury. Fund: Fundació Marató TV3, AGAUR and the ISCIII-EDRF. Keywords: Macrophage, Apoptosis inhibitor of macrophages, TGFB, Hepatic stellate cells, SMAD7 |
url |
http://www.sciencedirect.com/science/article/pii/S2352396419302919 |
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doaj-0e0f1fe152c2492b8c597665316ea9512020-11-25T01:57:03ZengElsevierEBioMedicine2352-39642019-05-0143513524CD5L is a pleiotropic player in liver fibrosis controlling damage, fibrosis and immune cell contentResearch in contextCristina Bárcena0Gemma Aran1Luís Perea2Lucía Sanjurjo3Érica Téllez4Anna Oncins5Helena Masnou6Isabel Serra7Mónica García-Gallo8Leonor Kremer9Margarita Sala10Carolina Armengol11Pau Sancho-Bru12Maria-Rosa Sarrias13Innate Immunity Group, Health Sciences Research Institute Germans Trias i Pujol (IGTP), Badalona, SpainInnate Immunity Group, Health Sciences Research Institute Germans Trias i Pujol (IGTP), Badalona, SpainInstitut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, SpainInnate Immunity Group, Health Sciences Research Institute Germans Trias i Pujol (IGTP), Badalona, Spain; Network for Biomedical Research in Diabetes and Associated Metabolic Disorders (CIBERDEM), SpainInnate Immunity Group, Health Sciences Research Institute Germans Trias i Pujol (IGTP), Badalona, SpainInnate Immunity Group, Health Sciences Research Institute Germans Trias i Pujol (IGTP), Badalona, SpainGastroenterology Dept., University Hospital Germans Trias i Pujol (HUGTiP), Badalona, SpainGastroenterology Dept., University Hospital Germans Trias i Pujol (HUGTiP), Badalona, SpainProtein Tools Unit and Department of Immunology and Oncology, Centro Nacional de Biotecnologia (CNB-CSIC), Madrid, SpainProtein Tools Unit and Department of Immunology and Oncology, Centro Nacional de Biotecnologia (CNB-CSIC), Madrid, SpainGastroenterology Dept., University Hospital Germans Trias i Pujol (HUGTiP), Badalona, Spain; Network for Biomedical Research in Hepatic and Digestive Diseases (CIBERehd), SpainNetwork for Biomedical Research in Hepatic and Digestive Diseases (CIBERehd), Spain; Childhood Liver Oncology Group, Program of Predictive and Personalized Medicine of Cancer (PMPCC), IGTP, SpainInstitut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Network for Biomedical Research in Hepatic and Digestive Diseases (CIBERehd), SpainInnate Immunity Group, Health Sciences Research Institute Germans Trias i Pujol (IGTP), Badalona, Spain; Network for Biomedical Research in Hepatic and Digestive Diseases (CIBERehd), Spain; Corresponding author at: Innate Immunity Group, Health Sciences Research Institute Germans Trias i Pujol. Ctra Can Ruti, Camí de les Escoles s/n, Edifici Muntanya, Planta 2, 08916 Badalona, Spain.Background: Chronic hepatic inflammation leads to liver fibrosis, which may progress to cirrhosis, a condition with high morbidity. Our aim was to assess the as yet unknown role of innate immunity protein CD5L in liver fibrosis. Methods: CD5L was measured by ELISA in plasma samples from cirrhotic (n = 63) and hepatitis (n = 39) patients, and healthy controls (n = 7), by immunohistochemistry in cirrhotic tissue (n = 12), and by quantitative RT-PCR in mouse liver cell subsets isolated by cell sorting. Recombinant CD5L (rCD5L) was administered into a murine model of CCl4-induced fibrosis, and damage, fibrosis and hepatic immune cell infiltration, including the LyC6hi (pro-fibrotic)-LyC6low (pro-resolutive) monocyte ratio were determined. Moreover, rCD5L was added into primary human hepatic stellate cells to study transforming growth factor β (TGFβ) activation responses. Findings: Cirrhotic patients showed elevated plasma CD5L concentrations as compared to patients with hepatitis and healthy controls (Mann-Whitney test p < 0·0001). Moreover, plasma CD5L correlated with disease progression, FIB4 fibrosis score (r:0·25, p < 0·0001) and tissue expression (r = 0·649; p = 0·022). Accordingly, CCl4-induced damage increased CD5L levels in total liver, particularly in hepatocytes and macrophages. rCD5L administration attenuated CCl4-induced injury and fibrosis as determined by reduced serum transaminase and collagen content. Moreover, rCD5L inhibited immune cell infiltration and promoted a phenotypic shift in monocytes from LyC6hi to LyC6low. Interestingly, rCD5L also had a direct effect on primary human hepatic stellate cells promoting SMAD7 expression, thus repressing TGFβ signalling. Interpretation: Our study identifies CD5L as a key pleiotropic inhibitor of chronic liver injury. Fund: Fundació Marató TV3, AGAUR and the ISCIII-EDRF. Keywords: Macrophage, Apoptosis inhibitor of macrophages, TGFB, Hepatic stellate cells, SMAD7http://www.sciencedirect.com/science/article/pii/S2352396419302919 |