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Microglia and meningeal macrophages depletion delays the onset of experimental autoimmune encephalomyelitis

In multiple sclerosis and the experimental autoimmune encephalomyelitis (EAE) model, both resident microglia and infiltrating macrophages contribute to demyelination as well as spontaneous remyelination. Nevertheless, the specific roles of microglia versus macrophages are unknown. We investigated th...

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Autores principales: Montilla, Alejandro, Zabala, Alazne, Er-Lukowiak, Marco, Rissiek, Björn, Magnus, Tim, Rodriguez-Iglesias, Noelia, Sierra, Amanda, Matute, Carlos, Domercq, María
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9835747/
https://www.ncbi.nlm.nih.gov/pubmed/36635255
http://dx.doi.org/10.1038/s41419-023-05551-3
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author Montilla, Alejandro
Zabala, Alazne
Er-Lukowiak, Marco
Rissiek, Björn
Magnus, Tim
Rodriguez-Iglesias, Noelia
Sierra, Amanda
Matute, Carlos
Domercq, María
author_facet Montilla, Alejandro
Zabala, Alazne
Er-Lukowiak, Marco
Rissiek, Björn
Magnus, Tim
Rodriguez-Iglesias, Noelia
Sierra, Amanda
Matute, Carlos
Domercq, María
author_sort Montilla, Alejandro
collection PubMed
description In multiple sclerosis and the experimental autoimmune encephalomyelitis (EAE) model, both resident microglia and infiltrating macrophages contribute to demyelination as well as spontaneous remyelination. Nevertheless, the specific roles of microglia versus macrophages are unknown. We investigated the influence of microglia in EAE using the colony stimulating factor 1 receptor (CSF-1R) inhibitor, PLX5622, to deplete microglial population and Ccr2(RFP/+) fms(EGFP/+) mice, to distinguish blood-derived macrophages from microglia. PLX5622 treatment depleted microglia and meningeal macrophages, and provoked a massive infiltration of CCR2(+) macrophages into demyelinating lesions and spinal cord parenchyma, albeit it did not alter EAE chronic phase. In contrast, microglia and meningeal macrophages depletion reduced the expression of major histocompatibility complex II and CD80 co-stimulatory molecule in dendritic cells, macrophages and microglia. In addition, it diminished T cell reactivation and proliferation in the spinal cord parenchyma, inducing a significant delay in EAE onset. Altogether, these data point to a specific role of CNS microglia and meningeal macrophages in antigen presentation and T cell reactivation at initial stages of EAE.
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spelling pubmed-98357472023-01-14 Microglia and meningeal macrophages depletion delays the onset of experimental autoimmune encephalomyelitis Montilla, Alejandro Zabala, Alazne Er-Lukowiak, Marco Rissiek, Björn Magnus, Tim Rodriguez-Iglesias, Noelia Sierra, Amanda Matute, Carlos Domercq, María Cell Death Dis Article In multiple sclerosis and the experimental autoimmune encephalomyelitis (EAE) model, both resident microglia and infiltrating macrophages contribute to demyelination as well as spontaneous remyelination. Nevertheless, the specific roles of microglia versus macrophages are unknown. We investigated the influence of microglia in EAE using the colony stimulating factor 1 receptor (CSF-1R) inhibitor, PLX5622, to deplete microglial population and Ccr2(RFP/+) fms(EGFP/+) mice, to distinguish blood-derived macrophages from microglia. PLX5622 treatment depleted microglia and meningeal macrophages, and provoked a massive infiltration of CCR2(+) macrophages into demyelinating lesions and spinal cord parenchyma, albeit it did not alter EAE chronic phase. In contrast, microglia and meningeal macrophages depletion reduced the expression of major histocompatibility complex II and CD80 co-stimulatory molecule in dendritic cells, macrophages and microglia. In addition, it diminished T cell reactivation and proliferation in the spinal cord parenchyma, inducing a significant delay in EAE onset. Altogether, these data point to a specific role of CNS microglia and meningeal macrophages in antigen presentation and T cell reactivation at initial stages of EAE. Nature Publishing Group UK 2023-01-12 /pmc/articles/PMC9835747/ /pubmed/36635255 http://dx.doi.org/10.1038/s41419-023-05551-3 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Montilla, Alejandro
Zabala, Alazne
Er-Lukowiak, Marco
Rissiek, Björn
Magnus, Tim
Rodriguez-Iglesias, Noelia
Sierra, Amanda
Matute, Carlos
Domercq, María
Microglia and meningeal macrophages depletion delays the onset of experimental autoimmune encephalomyelitis
title Microglia and meningeal macrophages depletion delays the onset of experimental autoimmune encephalomyelitis
title_full Microglia and meningeal macrophages depletion delays the onset of experimental autoimmune encephalomyelitis
title_fullStr Microglia and meningeal macrophages depletion delays the onset of experimental autoimmune encephalomyelitis
title_full_unstemmed Microglia and meningeal macrophages depletion delays the onset of experimental autoimmune encephalomyelitis
title_short Microglia and meningeal macrophages depletion delays the onset of experimental autoimmune encephalomyelitis
title_sort microglia and meningeal macrophages depletion delays the onset of experimental autoimmune encephalomyelitis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9835747/
https://www.ncbi.nlm.nih.gov/pubmed/36635255
http://dx.doi.org/10.1038/s41419-023-05551-3
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