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CD5L Promotes M2 Macrophage Polarization through Autophagy-Mediated Upregulation of ID3

CD5L (CD5 molecule-like) is a secreted glycoprotein that controls key mechanisms in inflammatory responses, with involvement in processes such as infection, atherosclerosis, and cancer. In macrophages, CD5L promotes an anti-inflammatory cytokine profile in response to TLR activation. In the present...

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Autores principales: Sanjurjo, Lucía, Aran, Gemma, Téllez, Érica, Amézaga, Núria, Armengol, Carolina, López, Daniel, Prats, Clara, Sarrias, Maria-Rosa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5858086/
https://www.ncbi.nlm.nih.gov/pubmed/29593730
http://dx.doi.org/10.3389/fimmu.2018.00480
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author Sanjurjo, Lucía
Aran, Gemma
Téllez, Érica
Amézaga, Núria
Armengol, Carolina
López, Daniel
Prats, Clara
Sarrias, Maria-Rosa
author_facet Sanjurjo, Lucía
Aran, Gemma
Téllez, Érica
Amézaga, Núria
Armengol, Carolina
López, Daniel
Prats, Clara
Sarrias, Maria-Rosa
author_sort Sanjurjo, Lucía
collection PubMed
description CD5L (CD5 molecule-like) is a secreted glycoprotein that controls key mechanisms in inflammatory responses, with involvement in processes such as infection, atherosclerosis, and cancer. In macrophages, CD5L promotes an anti-inflammatory cytokine profile in response to TLR activation. In the present study, we questioned whether CD5L is able to influence human macrophage plasticity, and drive its polarization toward any specific phenotype. We compared CD5L-induced phenotypic and functional changes to those caused by IFN/LPS, IL4, and IL10 in human monocytes. Phenotypic markers were quantified by RT-qPCR and flow cytometry, and a mathematical algorithm was built for their analysis. Moreover, we compared ROS production, phagocytic capacity, and inflammatory responses to LPS. CD5L drove cells toward a polarization similar to that induced by IL10. Furthermore, IL10- and CD5L-treated macrophages showed increased LC3-II content and colocalization with acidic compartments, thereby pointing to the enhancement of autophagy-dependent processes. Accordingly, siRNA targeting ATG7 in THP1 cells blocked CD5L-induced CD163 and Mer tyrosine kinase mRNA and efferocytosis. In these cells, gene expression profiling and validation indicated the upregulation of the transcription factor ID3 by CD5L through ATG7. In agreement, ID3 silencing reversed polarization by CD5L. Our data point to a significant contribution of CD5L-mediated autophagy to the induction of ID3 and provide the first evidence that CD5L drives macrophage polarization.
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spelling pubmed-58580862018-03-28 CD5L Promotes M2 Macrophage Polarization through Autophagy-Mediated Upregulation of ID3 Sanjurjo, Lucía Aran, Gemma Téllez, Érica Amézaga, Núria Armengol, Carolina López, Daniel Prats, Clara Sarrias, Maria-Rosa Front Immunol Immunology CD5L (CD5 molecule-like) is a secreted glycoprotein that controls key mechanisms in inflammatory responses, with involvement in processes such as infection, atherosclerosis, and cancer. In macrophages, CD5L promotes an anti-inflammatory cytokine profile in response to TLR activation. In the present study, we questioned whether CD5L is able to influence human macrophage plasticity, and drive its polarization toward any specific phenotype. We compared CD5L-induced phenotypic and functional changes to those caused by IFN/LPS, IL4, and IL10 in human monocytes. Phenotypic markers were quantified by RT-qPCR and flow cytometry, and a mathematical algorithm was built for their analysis. Moreover, we compared ROS production, phagocytic capacity, and inflammatory responses to LPS. CD5L drove cells toward a polarization similar to that induced by IL10. Furthermore, IL10- and CD5L-treated macrophages showed increased LC3-II content and colocalization with acidic compartments, thereby pointing to the enhancement of autophagy-dependent processes. Accordingly, siRNA targeting ATG7 in THP1 cells blocked CD5L-induced CD163 and Mer tyrosine kinase mRNA and efferocytosis. In these cells, gene expression profiling and validation indicated the upregulation of the transcription factor ID3 by CD5L through ATG7. In agreement, ID3 silencing reversed polarization by CD5L. Our data point to a significant contribution of CD5L-mediated autophagy to the induction of ID3 and provide the first evidence that CD5L drives macrophage polarization. Frontiers Media S.A. 2018-03-12 /pmc/articles/PMC5858086/ /pubmed/29593730 http://dx.doi.org/10.3389/fimmu.2018.00480 Text en Copyright © 2018 Sanjurjo, Aran, Téllez, Amézaga, Armengol, López, Prats and Sarrias. 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 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
Sanjurjo, Lucía
Aran, Gemma
Téllez, Érica
Amézaga, Núria
Armengol, Carolina
López, Daniel
Prats, Clara
Sarrias, Maria-Rosa
CD5L Promotes M2 Macrophage Polarization through Autophagy-Mediated Upregulation of ID3
title CD5L Promotes M2 Macrophage Polarization through Autophagy-Mediated Upregulation of ID3
title_full CD5L Promotes M2 Macrophage Polarization through Autophagy-Mediated Upregulation of ID3
title_fullStr CD5L Promotes M2 Macrophage Polarization through Autophagy-Mediated Upregulation of ID3
title_full_unstemmed CD5L Promotes M2 Macrophage Polarization through Autophagy-Mediated Upregulation of ID3
title_short CD5L Promotes M2 Macrophage Polarization through Autophagy-Mediated Upregulation of ID3
title_sort cd5l promotes m2 macrophage polarization through autophagy-mediated upregulation of id3
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5858086/
https://www.ncbi.nlm.nih.gov/pubmed/29593730
http://dx.doi.org/10.3389/fimmu.2018.00480
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