Characterization of the immune cell landscape of patients with NAFLD
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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, Jahrgang 15, Nr. 3, 2020, S. e0230307.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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 -