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Title: Endothelial-immune crosstalk contributes to vasculopathy in nonalcoholic fatty liver disease
Authors: Ng, Chun Yi
Lee, Khang Leng
Muthiah, Mark Dhinesh
Wu, Kan Xing
Chioh, Florence Wen Jing
Tan, Konstanze
Soon, Gwyneth Shook Ting
Shabbir, Asim
Loo, Wai Mun
Low, Zun Siong
Chen, Qingfeng
Tan, Nguan Soon
Ng, Huck-Hui
Dan, Yock Young
Cheung, Christine
Keywords: Science::Biological sciences
Issue Date: 2022
Source: Ng, C. Y., Lee, K. L., Muthiah, M. D., Wu, K. X., Chioh, F. W. J., Tan, K., Soon, G. S. T., Shabbir, A., Loo, W. M., Low, Z. S., Chen, Q., Tan, N. S., Ng, H., Dan, Y. Y. & Cheung, C. (2022). Endothelial-immune crosstalk contributes to vasculopathy in nonalcoholic fatty liver disease. EMBO Reports, 23(6), e54271-.
Project: H18/01/a0/017 
Journal: EMBO Reports 
Abstract: The top cause of mortality in patients with nonalcoholic fatty liver disease (NAFLD) is cardiovascular complications. However, mechanisms of NAFLD-associated vasculopathy remain understudied. Here, we show that blood outgrowth endothelial cells (BOECs) from NAFLD subjects exhibit global transcriptional upregulation of chemokines and human leukocyte antigens. In mouse models of diet-induced NAFLD, we confirm heightened endothelial expressions of CXCL12 in the aortas and the liver vasculatures, and increased retention of infiltrated leukocytes within the vessel walls. To elucidate endothelial-immune crosstalk, we performed immunoprofiling by single-cell analysis, uncovering T cell intensification in NAFLD patients. Functionally, treatment with a CXCL12-neutralizing antibody is effective at moderating the enhanced chemotactic effect of NAFLD BOECs in recruiting CD8+ T lymphocytes. Interference with the CXCL12-CXCR4 axis using a CXCR4 antagonist also averts the impact of immune cell transendothelial migration and restores endothelial barrier integrity. Clinically, we detect threefold more circulating damaged endothelial cells in NAFLD patients than in healthy controls. Our work provides insight into the modulation of interactions with effector immune cells to mitigate endothelial injury in NAFLD.
ISSN: 1469-221X
DOI: 10.15252/embr.202154271
Schools: School of Biological Sciences 
Lee Kong Chian School of Medicine (LKCMedicine) 
Organisations: National University of Singapore
Institute of Molecular and Cell Biology, A*STAR
Rights: © 2022 The Authors. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits useand distribution in any medium, provided the originalwork is properly cited, the use is non-commercial andno modifications or adaptations are made.
Fulltext Permission: open
Fulltext Availability: With Fulltext
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