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Chronic Liver Disease in Humans Causes Expansion and Differentiation of Liver Lymphatic Endothelial Cells
Liver lymphatic vessels support liver function by draining interstitial fluid, cholesterol, fat, and immune cells for surveillance in the liver draining lymph node. Chronic liver disease is associated with increased inflammation and immune cell infiltrate. However, it is currently unknown if or how...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6530422/ https://www.ncbi.nlm.nih.gov/pubmed/31156626 http://dx.doi.org/10.3389/fimmu.2019.01036 |
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author | Tamburini, Beth A. Jiron Finlon, Jeffrey M. Gillen, Austin E. Kriss, Michael S. Riemondy, Kent A. Fu, Rui Schuyler, Ronald P. Hesselberth, Jay R. Rosen, Hugo R. Burchill, Matthew A. |
author_facet | Tamburini, Beth A. Jiron Finlon, Jeffrey M. Gillen, Austin E. Kriss, Michael S. Riemondy, Kent A. Fu, Rui Schuyler, Ronald P. Hesselberth, Jay R. Rosen, Hugo R. Burchill, Matthew A. |
author_sort | Tamburini, Beth A. Jiron |
collection | PubMed |
description | Liver lymphatic vessels support liver function by draining interstitial fluid, cholesterol, fat, and immune cells for surveillance in the liver draining lymph node. Chronic liver disease is associated with increased inflammation and immune cell infiltrate. However, it is currently unknown if or how lymphatic vessels respond to increased inflammation and immune cell infiltrate in the liver during chronic disease. Here we demonstrate that lymphatic vessel abundance increases in patients with chronic liver disease and is associated with areas of fibrosis and immune cell infiltration. Using single-cell mRNA sequencing and multi-spectral immunofluorescence analysis we identified liver lymphatic endothelial cells and found that chronic liver disease results in lymphatic endothelial cells (LECs) that are in active cell cycle with increased expression of CCL21. Additionally, we found that LECs from patients with NASH adopt a transcriptional program associated with increased IL13 signaling. Moreover, we found that oxidized low density lipoprotein, associated with NASH pathogenesis, induced the transcription and protein production of IL13 in LECs both in vitro and in a mouse model. Finally, we show that oxidized low density lipoprotein reduced the transcription of PROX1 and decreased lymphatic stability. Together these data indicate that LECs are active participants in the liver, expanding in an attempt to maintain tissue homeostasis. However, when inflammatory signals, such as oxidized low density lipoprotein are increased, as in NASH, lymphatic function declines and liver homeostasis is impeded. |
format | Online Article Text |
id | pubmed-6530422 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-65304222019-05-31 Chronic Liver Disease in Humans Causes Expansion and Differentiation of Liver Lymphatic Endothelial Cells Tamburini, Beth A. Jiron Finlon, Jeffrey M. Gillen, Austin E. Kriss, Michael S. Riemondy, Kent A. Fu, Rui Schuyler, Ronald P. Hesselberth, Jay R. Rosen, Hugo R. Burchill, Matthew A. Front Immunol Immunology Liver lymphatic vessels support liver function by draining interstitial fluid, cholesterol, fat, and immune cells for surveillance in the liver draining lymph node. Chronic liver disease is associated with increased inflammation and immune cell infiltrate. However, it is currently unknown if or how lymphatic vessels respond to increased inflammation and immune cell infiltrate in the liver during chronic disease. Here we demonstrate that lymphatic vessel abundance increases in patients with chronic liver disease and is associated with areas of fibrosis and immune cell infiltration. Using single-cell mRNA sequencing and multi-spectral immunofluorescence analysis we identified liver lymphatic endothelial cells and found that chronic liver disease results in lymphatic endothelial cells (LECs) that are in active cell cycle with increased expression of CCL21. Additionally, we found that LECs from patients with NASH adopt a transcriptional program associated with increased IL13 signaling. Moreover, we found that oxidized low density lipoprotein, associated with NASH pathogenesis, induced the transcription and protein production of IL13 in LECs both in vitro and in a mouse model. Finally, we show that oxidized low density lipoprotein reduced the transcription of PROX1 and decreased lymphatic stability. Together these data indicate that LECs are active participants in the liver, expanding in an attempt to maintain tissue homeostasis. However, when inflammatory signals, such as oxidized low density lipoprotein are increased, as in NASH, lymphatic function declines and liver homeostasis is impeded. Frontiers Media S.A. 2019-05-15 /pmc/articles/PMC6530422/ /pubmed/31156626 http://dx.doi.org/10.3389/fimmu.2019.01036 Text en Copyright © 2019 Tamburini, Finlon, Gillen, Kriss, Riemondy, Fu, Schuyler, Hesselberth, Rosen and Burchill. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Tamburini, Beth A. Jiron Finlon, Jeffrey M. Gillen, Austin E. Kriss, Michael S. Riemondy, Kent A. Fu, Rui Schuyler, Ronald P. Hesselberth, Jay R. Rosen, Hugo R. Burchill, Matthew A. Chronic Liver Disease in Humans Causes Expansion and Differentiation of Liver Lymphatic Endothelial Cells |
title | Chronic Liver Disease in Humans Causes Expansion and Differentiation of Liver Lymphatic Endothelial Cells |
title_full | Chronic Liver Disease in Humans Causes Expansion and Differentiation of Liver Lymphatic Endothelial Cells |
title_fullStr | Chronic Liver Disease in Humans Causes Expansion and Differentiation of Liver Lymphatic Endothelial Cells |
title_full_unstemmed | Chronic Liver Disease in Humans Causes Expansion and Differentiation of Liver Lymphatic Endothelial Cells |
title_short | Chronic Liver Disease in Humans Causes Expansion and Differentiation of Liver Lymphatic Endothelial Cells |
title_sort | chronic liver disease in humans causes expansion and differentiation of liver lymphatic endothelial cells |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6530422/ https://www.ncbi.nlm.nih.gov/pubmed/31156626 http://dx.doi.org/10.3389/fimmu.2019.01036 |
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