FLT3/FLT3L-mediated CD103+ dendritic cells alleviates hepatic ischemia-reperfusion injury in mice via activation of treg cells

Chun-ze Zhou; Rui-feng Wang; De-lei Cheng; Yi-jiang Zhu; Qi Cao; Wei-fu Lv

Biomedicine & Pharmacotherapy (Oct 2019)

FLT3/FLT3L-mediated CD103+ dendritic cells alleviates hepatic ischemia-reperfusion injury in mice via activation of treg cells

Chun-ze Zhou,
Rui-feng Wang,
De-lei Cheng,
Yi-jiang Zhu,
Qi Cao,
Wei-fu Lv

Affiliations

Chun-ze Zhou: Medical College of Shandong University, Jinan, Shandong, 250021, PR China; Interventional radiology department, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, PR China
Rui-feng Wang: Nephrology Department, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230001, PR China
De-lei Cheng: Interventional radiology department, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, PR China
Yi-jiang Zhu: Interventional radiology department, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, PR China
Qi Cao: Centre for Transplant and Renal Research, Westmead Millennium Institute, University of Sydney, NSW, 2145, Australia
Wei-fu Lv: Interventional radiology department, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, PR China; Corresponding author at: Interventional radiology department, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, No. 17 Lujiang Road, Luyang District, Hefei, Anhui, 230001, PR China.

Journal volume & issue: Vol. 118

Abstract

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Background: This study was conducted to investigate the protective effect of Fms-like tyrosine kinase 3 (FLT3)/FLT3 ligand (FLT3L)-dependent CD103+ dendritic cells (DCs) on hepatic ischemia-reperfusion injury (IRI). Methods: A mouse model of hepatic IRI and cellular model following hypoxia-reperfusion (H/R) treatment were established. Peripheral blood and liver tissues were obtained and analyzed by flow cytometer in terms of percentage of CD103+DCs and regulatory T (Treg) cells. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were determined to assess liver function. Moreover, pro-inflammatory cytokines levels including tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were measured using enzyme-linked immunosorbent assay (ELISA). The histological morphology of liver tissues was examined with hematoxylin and eosin (HE) staining. The apoptosis was detected by terminal deoxynucleotidyl transferase (TdT) dUTP Nick End Labeling (TUNEL) assay. Treg-associated cytokines transforming growth factor (TGF)-β and IL-10 expressions were measured using quantitative real time polymerase chain reaction (qRT-PCR). Results: CD103+ DCs were significantly decreased in peripheral blood and liver tissues of mouse model of hepatic IRI. In vivo experiments indicated that CD103+ DCs infusion ameliorated IRI-induced liver damage and Treg inhibition. Further investigations demonstrated that FLT3/FLT3L-dependent CD103+ DCs suppressed hepatocyte apoptosis via activation of Treg cells in vitro. Conclusion: FLT3/FLT3L-induced CD103+ DCs alleviated hepatic IRI through activating Treg cells.

Published in Biomedicine & Pharmacotherapy

ISSN: 0753-3322 (Print); 1950-6007 (Online)
Publisher: Elsevier
Country of publisher: France
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.journals.elsevier.com/biomedicine-and-pharmacotherapy

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