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CD8 signaling in microglia/macrophage M1 polarization in a rat model of cerebral ischemia
Classical or M1 activity of microglia/macrophages has been described in several neurodegenerative and brain inflammatory conditions and has also been linked to expansion of ischemic injury in post-stroke brain. While different pathways of M1 polarization have been suggested to occur in the post-stro...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5771556/ https://www.ncbi.nlm.nih.gov/pubmed/29342151 http://dx.doi.org/10.1371/journal.pone.0186937 |
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author | Boddaert, Jan Bielen, Kenny ’s Jongers, Bart Manocha, Ekta Yperzeele, Laetitia Cras, Patrick Pirici, Daniel Kumar-Singh, Samir |
author_facet | Boddaert, Jan Bielen, Kenny ’s Jongers, Bart Manocha, Ekta Yperzeele, Laetitia Cras, Patrick Pirici, Daniel Kumar-Singh, Samir |
author_sort | Boddaert, Jan |
collection | PubMed |
description | Classical or M1 activity of microglia/macrophages has been described in several neurodegenerative and brain inflammatory conditions and has also been linked to expansion of ischemic injury in post-stroke brain. While different pathways of M1 polarization have been suggested to occur in the post-stroke brain, the precise underlying mechanisms remain undefined. Using a transient middle cerebral artery occlusion (MCAO) rat model, we showed a progressive M2 to M1 polarization in the perilesional brain region with M1 cells becoming one of the dominant subsets by day 4 post-stroke. Comparing key receptors involved in M1 polarization (CD8, IFNγR, Clec4, FcγR, TLR3 and TLR4) and their signal transducers (Syk, Stat1, Irf3, and Traf6) at the day 4 time point, we showed a strong upregulation of CD8 along with SYK transducer in dissected perilesional brain tissue. We further showed that CD8 expression in the post-stroke brain was associated with activated (CD68+) macrophages and that progressive accumulation of CD8+CD68+ cells in the post-stroke brain coincided with increased iNOS (M1 marker) and reduced Arg1 (M2 marker) expression on these cells. In vitro ligand-based stimulation of the CD8 receptor caused increased iNOS expression and an enhanced capacity to phagocytose E. coli particles; and interestingly, CD8 stimulation was also able to repolarize IL4-treated M2 cells to an M1 phenotype. Our data suggest that increased CD8 signaling in the post-stroke brain is primarily associated with microglia/macrophages and can independently drive M1 polarization, and that modulation of CD8 signaling could be a potential target to limit secondary post-stroke brain damage. |
format | Online Article Text |
id | pubmed-5771556 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-57715562018-01-23 CD8 signaling in microglia/macrophage M1 polarization in a rat model of cerebral ischemia Boddaert, Jan Bielen, Kenny ’s Jongers, Bart Manocha, Ekta Yperzeele, Laetitia Cras, Patrick Pirici, Daniel Kumar-Singh, Samir PLoS One Research Article Classical or M1 activity of microglia/macrophages has been described in several neurodegenerative and brain inflammatory conditions and has also been linked to expansion of ischemic injury in post-stroke brain. While different pathways of M1 polarization have been suggested to occur in the post-stroke brain, the precise underlying mechanisms remain undefined. Using a transient middle cerebral artery occlusion (MCAO) rat model, we showed a progressive M2 to M1 polarization in the perilesional brain region with M1 cells becoming one of the dominant subsets by day 4 post-stroke. Comparing key receptors involved in M1 polarization (CD8, IFNγR, Clec4, FcγR, TLR3 and TLR4) and their signal transducers (Syk, Stat1, Irf3, and Traf6) at the day 4 time point, we showed a strong upregulation of CD8 along with SYK transducer in dissected perilesional brain tissue. We further showed that CD8 expression in the post-stroke brain was associated with activated (CD68+) macrophages and that progressive accumulation of CD8+CD68+ cells in the post-stroke brain coincided with increased iNOS (M1 marker) and reduced Arg1 (M2 marker) expression on these cells. In vitro ligand-based stimulation of the CD8 receptor caused increased iNOS expression and an enhanced capacity to phagocytose E. coli particles; and interestingly, CD8 stimulation was also able to repolarize IL4-treated M2 cells to an M1 phenotype. Our data suggest that increased CD8 signaling in the post-stroke brain is primarily associated with microglia/macrophages and can independently drive M1 polarization, and that modulation of CD8 signaling could be a potential target to limit secondary post-stroke brain damage. Public Library of Science 2018-01-17 /pmc/articles/PMC5771556/ /pubmed/29342151 http://dx.doi.org/10.1371/journal.pone.0186937 Text en © 2018 Boddaert et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Boddaert, Jan Bielen, Kenny ’s Jongers, Bart Manocha, Ekta Yperzeele, Laetitia Cras, Patrick Pirici, Daniel Kumar-Singh, Samir CD8 signaling in microglia/macrophage M1 polarization in a rat model of cerebral ischemia |
title | CD8 signaling in microglia/macrophage M1 polarization in a rat model of cerebral ischemia |
title_full | CD8 signaling in microglia/macrophage M1 polarization in a rat model of cerebral ischemia |
title_fullStr | CD8 signaling in microglia/macrophage M1 polarization in a rat model of cerebral ischemia |
title_full_unstemmed | CD8 signaling in microglia/macrophage M1 polarization in a rat model of cerebral ischemia |
title_short | CD8 signaling in microglia/macrophage M1 polarization in a rat model of cerebral ischemia |
title_sort | cd8 signaling in microglia/macrophage m1 polarization in a rat model of cerebral ischemia |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5771556/ https://www.ncbi.nlm.nih.gov/pubmed/29342151 http://dx.doi.org/10.1371/journal.pone.0186937 |
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