Liver fibrosis and CD206

ALT, alanine aminotransferase BAMBI, BMP and Activin Membrane-bound Inhibitor CD206+ macrophages DAA, direct-acting antiviral DC, dendritic cell FFPE, formalin-fixed paraffin-embedded GM-CSF GM-CSF, granulocyte-macrophage colony-stimulating factor HCC, hepatocellular carcinoma HCV HIER, heat-induced epitope retrieval HSC, hepatic stellate cells ICS, intracellular cytokine staining Intrahepatic macrophages LPS, lipopolysaccharide LSM, liver stiffness measurement MS, multiple sclerosis NASH NASH, non-alcoholic steatohepatitis PBMCs, peripheral blood mononuclear cells RA, rheumatoid arthritis SVR, sustained virological response TCR, T cell receptor TMA, tissue microarray TNFα, tumour necrosis factor-α TSA, tyramide signal amplification anti-GM-CSF neutralizing antibody fibrosis moMΦs, monocyte-derived macrophage-like cells t-SNE, t-distributed stochastic neighbour embedding

Journal

JHEP reports : innovation in hepatology
ISSN: 2589-5559
Titre abrégé: JHEP Rep
Pays: Netherlands
ID NLM: 101761237

Informations de publication

Date de publication:
Feb 2020
Historique:
received: 22 08 2019
revised: 18 11 2019
accepted: 20 11 2019
entrez: 11 2 2020
pubmed: 11 2 2020
medline: 11 2 2020
Statut: epublish

Résumé

Chronic liver inflammation leads to fibrosis and cirrhosis and is associated with an accumulation of intrahepatic TNFα-secreting CD206 Liver immunohistochemistry and serum quantification were performed in patients with viral and non-viral-related liver disease to compare CD206 Using multiplex immunofluorescence and histo-cytometry, we show that highly fibrotic livers had a greater density of CD206 While the direct involvement of CD206 Liver fibrosis is a major driver of liver disease progression. Herein, we have shown that granulocyte-macrophage colony-stimulating factor (GM-CSF) plays an important role in the development of liver fibrosis. Our findings support the use of anti-GM-CSF neutralising antibodies for the management of patients with chronic liver disease resulting from both viral and non-viral causes.

Sections du résumé

BACKGROUND & AIMS OBJECTIVE
Chronic liver inflammation leads to fibrosis and cirrhosis and is associated with an accumulation of intrahepatic TNFα-secreting CD206
METHODS METHODS
Liver immunohistochemistry and serum quantification were performed in patients with viral and non-viral-related liver disease to compare CD206
RESULTS RESULTS
Using multiplex immunofluorescence and histo-cytometry, we show that highly fibrotic livers had a greater density of CD206
CONCLUSIONS CONCLUSIONS
While the direct involvement of CD206
LAY SUMMARY BACKGROUND
Liver fibrosis is a major driver of liver disease progression. Herein, we have shown that granulocyte-macrophage colony-stimulating factor (GM-CSF) plays an important role in the development of liver fibrosis. Our findings support the use of anti-GM-CSF neutralising antibodies for the management of patients with chronic liver disease resulting from both viral and non-viral causes.

Identifiants

pubmed: 32039403
doi: 10.1016/j.jhepr.2019.11.006
pii: S2589-5559(19)30156-9
pii: 100062
pmc: PMC7005658
doi:

Types de publication

Journal Article

Langues

eng

Pagination

100062

Informations de copyright

© 2019 The Author(s).

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Auteurs

Alfonso Tan-Garcia (A)

Program in Emerging Infectious Diseases, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore.

Fritz Lai (F)

Humanised Mouse Unit, Institute of Molecular and Cell Biology, ASTAR, 61 Biopolis Drive, Singapore 138673, Singapore.

Joe Poh Sheng Yeong (JP)

Department of Anatomical Pathology, Singapore General Hospital, Singapore.

Sergio E Irac (SE)

Program in Emerging Infectious Diseases, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore.

Pei Y Ng (PY)

Singapore Immunology Network, ASTAR, 8A Biomedical Grove, Immunos Building, Level 4, Singapore 138648, Singapore.

Rasha Msallam (R)

Singapore Immunology Network, ASTAR, 8A Biomedical Grove, Immunos Building, Level 4, Singapore 138648, Singapore.

Jeffrey Chun Tatt Lim (JC)

Department of Anatomical Pathology, Singapore General Hospital, Singapore.

Lu-En Wai (LE)

Program in Emerging Infectious Diseases, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore.

Christine Y L Tham (CYL)

Program in Emerging Infectious Diseases, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore.

Su P Choo (SP)

Department of Medical Oncology, National Cancer Centre, Singapore.

Tony Lim (T)

Department of Anatomical Pathology, Singapore General Hospital, Singapore.

Dan Y Young (DY)

Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Gastroenterology and Hepatology, National University Hospital, National University Health System, Singapore.

Roberta D'Ambrosio (R)

CRC "A.M. e A. Migliavacca" Center for the Study of Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, Italy.

Elisabetta Degasperi (E)

CRC "A.M. e A. Migliavacca" Center for the Study of Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, Italy.

Riccardo Perbellini (R)

CRC "A.M. e A. Migliavacca" Center for the Study of Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, Italy.

Evan Newell (E)

Singapore Immunology Network, ASTAR, 8A Biomedical Grove, Immunos Building, Level 4, Singapore 138648, Singapore.
Fred Hutch Cancer Research Center, Vaccine and Infectious Disease Division, Seattle, WA, USA.

Nina Le Bert (N)

Program in Emerging Infectious Diseases, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore.

Florent Ginhoux (F)

Singapore Immunology Network, ASTAR, 8A Biomedical Grove, Immunos Building, Level 4, Singapore 138648, Singapore.

Antonio Bertoletti (A)

Program in Emerging Infectious Diseases, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore.
Singapore Immunology Network, ASTAR, 8A Biomedical Grove, Immunos Building, Level 4, Singapore 138648, Singapore.

Qingfeng Chen (Q)

Humanised Mouse Unit, Institute of Molecular and Cell Biology, ASTAR, 61 Biopolis Drive, Singapore 138673, Singapore.
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 119228, Singapore.

Charles-Antoine Dutertre (CA)

Program in Emerging Infectious Diseases, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore.
Singapore Immunology Network, ASTAR, 8A Biomedical Grove, Immunos Building, Level 4, Singapore 138648, Singapore.

Classifications MeSH