CX3CR1 differentiates F4/80low monocytes into pro-inflammatory F4/80high macrophages in the liver

Abstract The expression of chemokine receptor CX3CR1 is related to migration and signaling in cells of the monocyte-macrophage lineage. The precise roles of CX3CR1 in the liver have been investigated but not clearly elucidated. Here, we investigated the roles of CX3CR1 in hepatic macrophages and liv...

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Autores principales:	Young-Sun Lee, Myung-Ho Kim, Hyon-Seung Yi, So Yeon Kim, Hee-Hoon Kim, Ji Hoon Kim, Jong Eun Yeon, Kwan Soo Byun, Jin-Seok Byun, Won-Il Jeong
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Human Umbilical Vein Endothelial Cells (HUVECs) Liver Sinusoidal Endothelial Cells (LSECs) Clodronate Liposome Treatment Macrophage Subsets CX3CR1 Expression Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bd9bdcd8b9be49999ee286a46066b5f3
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spelling	oai:doaj.org-article:bd9bdcd8b9be49999ee286a46066b5f32021-12-02T15:08:13ZCX3CR1 differentiates F4/80low monocytes into pro-inflammatory F4/80high macrophages in the liver10.1038/s41598-018-33440-92045-2322https://doaj.org/article/bd9bdcd8b9be49999ee286a46066b5f32018-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-33440-9https://doaj.org/toc/2045-2322Abstract The expression of chemokine receptor CX3CR1 is related to migration and signaling in cells of the monocyte-macrophage lineage. The precise roles of CX3CR1 in the liver have been investigated but not clearly elucidated. Here, we investigated the roles of CX3CR1 in hepatic macrophages and liver injury. Hepatic and splenic CX3CR1lowF4/80low monocytes and CX3CR1lowCD16− monocytes were differentiated into CX3CR1highF4/80high or CX3CR1highCD16+ macrophages by co-culture with endothelial cells. Moreover, CX3CL1 deficiency in human umbilical vein endothelial cells (HUVECs) attenuated the expression of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), whereas recombinant CX3CL1 treatment reversed this expression in co-cultured monocytes. Upon treatment with clodronate liposome, hepatic F4/80high macrophages were successfully depleted at day 2 and recovered similarly in CX3CR1+/GFP and CX3CR1GFP/GFP mice at week 4, suggesting a CX3CR1-independent replacement. However, F4/80high macrophages of CX3CR1+/GFP showed a stronger pro-inflammatory phenotype than CX3CR1GFP/GFP mice. In clodronate-treated chimeric CX3CR1+/GFP and CX3CR1GFP/GFP mice, CX3CR1+F4/80high macrophages showed higher expression of IL-1β and TNF-α than CX3CR1−F4/80high macrophages. In alcoholic liver injury, despite the similar frequency of hepatic F4/80high macrophages, CX3CR1GFP/GFP mice showed reduced liver injury, hepatic fat accumulation, and inflammatory responses than CX3CR1+/GFP mice. Thus, CX3CR1 could be a novel therapeutic target for pro-inflammatory macrophage-mediated liver injury.Young-Sun LeeMyung-Ho KimHyon-Seung YiSo Yeon KimHee-Hoon KimJi Hoon KimJong Eun YeonKwan Soo ByunJin-Seok ByunWon-Il JeongNature PortfolioarticleHuman Umbilical Vein Endothelial Cells (HUVECs)Liver Sinusoidal Endothelial Cells (LSECs)Clodronate Liposome TreatmentMacrophage SubsetsCX3CR1 ExpressionMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-13 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Human Umbilical Vein Endothelial Cells (HUVECs) Liver Sinusoidal Endothelial Cells (LSECs) Clodronate Liposome Treatment Macrophage Subsets CX3CR1 Expression Medicine R Science Q
spellingShingle	Human Umbilical Vein Endothelial Cells (HUVECs) Liver Sinusoidal Endothelial Cells (LSECs) Clodronate Liposome Treatment Macrophage Subsets CX3CR1 Expression Medicine R Science Q Young-Sun Lee Myung-Ho Kim Hyon-Seung Yi So Yeon Kim Hee-Hoon Kim Ji Hoon Kim Jong Eun Yeon Kwan Soo Byun Jin-Seok Byun Won-Il Jeong CX3CR1 differentiates F4/80low monocytes into pro-inflammatory F4/80high macrophages in the liver
description	Abstract The expression of chemokine receptor CX3CR1 is related to migration and signaling in cells of the monocyte-macrophage lineage. The precise roles of CX3CR1 in the liver have been investigated but not clearly elucidated. Here, we investigated the roles of CX3CR1 in hepatic macrophages and liver injury. Hepatic and splenic CX3CR1lowF4/80low monocytes and CX3CR1lowCD16− monocytes were differentiated into CX3CR1highF4/80high or CX3CR1highCD16+ macrophages by co-culture with endothelial cells. Moreover, CX3CL1 deficiency in human umbilical vein endothelial cells (HUVECs) attenuated the expression of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), whereas recombinant CX3CL1 treatment reversed this expression in co-cultured monocytes. Upon treatment with clodronate liposome, hepatic F4/80high macrophages were successfully depleted at day 2 and recovered similarly in CX3CR1+/GFP and CX3CR1GFP/GFP mice at week 4, suggesting a CX3CR1-independent replacement. However, F4/80high macrophages of CX3CR1+/GFP showed a stronger pro-inflammatory phenotype than CX3CR1GFP/GFP mice. In clodronate-treated chimeric CX3CR1+/GFP and CX3CR1GFP/GFP mice, CX3CR1+F4/80high macrophages showed higher expression of IL-1β and TNF-α than CX3CR1−F4/80high macrophages. In alcoholic liver injury, despite the similar frequency of hepatic F4/80high macrophages, CX3CR1GFP/GFP mice showed reduced liver injury, hepatic fat accumulation, and inflammatory responses than CX3CR1+/GFP mice. Thus, CX3CR1 could be a novel therapeutic target for pro-inflammatory macrophage-mediated liver injury.
format	article
author	Young-Sun Lee Myung-Ho Kim Hyon-Seung Yi So Yeon Kim Hee-Hoon Kim Ji Hoon Kim Jong Eun Yeon Kwan Soo Byun Jin-Seok Byun Won-Il Jeong
author_facet	Young-Sun Lee Myung-Ho Kim Hyon-Seung Yi So Yeon Kim Hee-Hoon Kim Ji Hoon Kim Jong Eun Yeon Kwan Soo Byun Jin-Seok Byun Won-Il Jeong
author_sort	Young-Sun Lee
title	CX3CR1 differentiates F4/80low monocytes into pro-inflammatory F4/80high macrophages in the liver
title_short	CX3CR1 differentiates F4/80low monocytes into pro-inflammatory F4/80high macrophages in the liver
title_full	CX3CR1 differentiates F4/80low monocytes into pro-inflammatory F4/80high macrophages in the liver
title_fullStr	CX3CR1 differentiates F4/80low monocytes into pro-inflammatory F4/80high macrophages in the liver
title_full_unstemmed	CX3CR1 differentiates F4/80low monocytes into pro-inflammatory F4/80high macrophages in the liver
title_sort	cx3cr1 differentiates f4/80low monocytes into pro-inflammatory f4/80high macrophages in the liver
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/bd9bdcd8b9be49999ee286a46066b5f3
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CX3CR1 differentiates F4/80low monocytes into pro-inflammatory F4/80high macrophages in the liver

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