Characterization of the immune cell landscape of patients with NAFLD

Standard

Characterization of the immune cell landscape of patients with NAFLD. / Diedrich, Tom; Kummer, Silke; Galante, Antonio; Drolz, Andreas; Schlicker, Veronika; Lohse, Ansgar W; Kluwe, Johannes; Eberhard, Johanna Maria; Schulze Zur Wiesch, Julian.

In: PLOS ONE, Vol. 15, No. 3, 2020, p. e0230307.

Research output: SCORING: Contribution to journalSCORING: Journal articleResearchpeer-review

Harvard

APA

Vancouver

Bibtex

@article{80f4d4d85b234d37a6f7891543c8cfc1,
title = "Characterization of the immune cell landscape of patients with NAFLD",
abstract = "Multiple factors are involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), but the exact immunological mechanisms that cause inflammation and fibrosis of the liver remain enigmatic. In this current study, cellular samples of a cohort of NAFLD patients (peripheral blood mononuclear cells (PBMC): n = 27, liver samples: n = 15) and healthy individuals (PBMC: n = 26, liver samples: n = 3) were analyzed using 16-color flow cytometry, and the frequency and phenotype of 23 immune cell subtypes was assessed. PBMC of NAFLD patients showed decreased frequencies of total CD3+, CD8+ T cells, CD56dim NK cells and MAIT cells, but elevated frequencies of CD4+ T cells and Th2 cells compared to healthy controls. Intrahepatic lymphocytes (IHL) of NAFLD patients showed decreased frequencies of total T cells, total CD8+ T cells, Vd2+γδ T cells, and CD56bright NK cells, but elevated frequencies of Vδ2-γδ T cells and CD56dim NK cells compared to healthy controls. The activating receptor NKG2D was significantly less frequently expressed among iNKT cells, total NK cells and CD56dim NK cells of PBMC of NAFLD patients compared to healthy controls. More strikingly, hepatic fibrosis as measured by fibroscan elastography negatively correlated with the intrahepatic frequency of total NK cells (r2 = 0,3737, p = 0,02). Hepatic steatosis as measured by controlled attenuation parameter (CAP) value negatively correlated with the frequency of circulating NKG2D+ iNKT cells (r2 = 0,3365, p = 0,0047). Our data provide an overview of the circulating and intrahepatic immune cell composition of NAFLD patients, and point towards a potential role of NK cells and iNKT cells for the regulation of hepatic fibrosis and steatosis in NAFLD.",
keywords = "Adult, Biopsy, CD3 Complex/blood, CD56 Antigen/blood, CD8-Positive T-Lymphocytes/immunology, Elasticity Imaging Techniques, Female, Flow Cytometry, Humans, Immunophenotyping, Inflammation/blood, Killer Cells, Natural/immunology, Leukocytes, Mononuclear/immunology, Liver/diagnostic imaging, Liver Cirrhosis/blood, Male, Middle Aged, NK Cell Lectin-Like Receptor Subfamily K/blood, Non-alcoholic Fatty Liver Disease/blood, Th2 Cells/immunology",
author = "Tom Diedrich and Silke Kummer and Antonio Galante and Andreas Drolz and Veronika Schlicker and Lohse, {Ansgar W} and Johannes Kluwe and Eberhard, {Johanna Maria} and {Schulze Zur Wiesch}, Julian",
year = "2020",
doi = "10.1371/journal.pone.0230307",
language = "English",
volume = "15",
pages = "e0230307",
journal = "PLOS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "3",

}

RIS

TY - JOUR

T1 - Characterization of the immune cell landscape of patients with NAFLD

AU - Diedrich, Tom

AU - Kummer, Silke

AU - Galante, Antonio

AU - Drolz, Andreas

AU - Schlicker, Veronika

AU - Lohse, Ansgar W

AU - Kluwe, Johannes

AU - Eberhard, Johanna Maria

AU - Schulze Zur Wiesch, Julian

PY - 2020

Y1 - 2020

N2 - Multiple factors are involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), but the exact immunological mechanisms that cause inflammation and fibrosis of the liver remain enigmatic. In this current study, cellular samples of a cohort of NAFLD patients (peripheral blood mononuclear cells (PBMC): n = 27, liver samples: n = 15) and healthy individuals (PBMC: n = 26, liver samples: n = 3) were analyzed using 16-color flow cytometry, and the frequency and phenotype of 23 immune cell subtypes was assessed. PBMC of NAFLD patients showed decreased frequencies of total CD3+, CD8+ T cells, CD56dim NK cells and MAIT cells, but elevated frequencies of CD4+ T cells and Th2 cells compared to healthy controls. Intrahepatic lymphocytes (IHL) of NAFLD patients showed decreased frequencies of total T cells, total CD8+ T cells, Vd2+γδ T cells, and CD56bright NK cells, but elevated frequencies of Vδ2-γδ T cells and CD56dim NK cells compared to healthy controls. The activating receptor NKG2D was significantly less frequently expressed among iNKT cells, total NK cells and CD56dim NK cells of PBMC of NAFLD patients compared to healthy controls. More strikingly, hepatic fibrosis as measured by fibroscan elastography negatively correlated with the intrahepatic frequency of total NK cells (r2 = 0,3737, p = 0,02). Hepatic steatosis as measured by controlled attenuation parameter (CAP) value negatively correlated with the frequency of circulating NKG2D+ iNKT cells (r2 = 0,3365, p = 0,0047). Our data provide an overview of the circulating and intrahepatic immune cell composition of NAFLD patients, and point towards a potential role of NK cells and iNKT cells for the regulation of hepatic fibrosis and steatosis in NAFLD.

AB - Multiple factors are involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), but the exact immunological mechanisms that cause inflammation and fibrosis of the liver remain enigmatic. In this current study, cellular samples of a cohort of NAFLD patients (peripheral blood mononuclear cells (PBMC): n = 27, liver samples: n = 15) and healthy individuals (PBMC: n = 26, liver samples: n = 3) were analyzed using 16-color flow cytometry, and the frequency and phenotype of 23 immune cell subtypes was assessed. PBMC of NAFLD patients showed decreased frequencies of total CD3+, CD8+ T cells, CD56dim NK cells and MAIT cells, but elevated frequencies of CD4+ T cells and Th2 cells compared to healthy controls. Intrahepatic lymphocytes (IHL) of NAFLD patients showed decreased frequencies of total T cells, total CD8+ T cells, Vd2+γδ T cells, and CD56bright NK cells, but elevated frequencies of Vδ2-γδ T cells and CD56dim NK cells compared to healthy controls. The activating receptor NKG2D was significantly less frequently expressed among iNKT cells, total NK cells and CD56dim NK cells of PBMC of NAFLD patients compared to healthy controls. More strikingly, hepatic fibrosis as measured by fibroscan elastography negatively correlated with the intrahepatic frequency of total NK cells (r2 = 0,3737, p = 0,02). Hepatic steatosis as measured by controlled attenuation parameter (CAP) value negatively correlated with the frequency of circulating NKG2D+ iNKT cells (r2 = 0,3365, p = 0,0047). Our data provide an overview of the circulating and intrahepatic immune cell composition of NAFLD patients, and point towards a potential role of NK cells and iNKT cells for the regulation of hepatic fibrosis and steatosis in NAFLD.

KW - Adult

KW - Biopsy

KW - CD3 Complex/blood

KW - CD56 Antigen/blood

KW - CD8-Positive T-Lymphocytes/immunology

KW - Elasticity Imaging Techniques

KW - Female

KW - Flow Cytometry

KW - Humans

KW - Immunophenotyping

KW - Inflammation/blood

KW - Killer Cells, Natural/immunology

KW - Leukocytes, Mononuclear/immunology

KW - Liver/diagnostic imaging

KW - Liver Cirrhosis/blood

KW - Male

KW - Middle Aged

KW - NK Cell Lectin-Like Receptor Subfamily K/blood

KW - Non-alcoholic Fatty Liver Disease/blood

KW - Th2 Cells/immunology

U2 - 10.1371/journal.pone.0230307

DO - 10.1371/journal.pone.0230307

M3 - SCORING: Journal article

C2 - 32168345

VL - 15

SP - e0230307

JO - PLOS ONE

JF - PLOS ONE

SN - 1932-6203

IS - 3

ER -