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Differential roles of microglia and monocytes in the inflamed central nervous system

In the human disorder multiple sclerosis (MS) and in the model experimental autoimmune encephalomyelitis (EAE), macrophages predominate in demyelinated areas and their numbers correlate to tissue damage. Macrophages may be derived from infiltrating monocytes or resident microglia, yet are indistingu...

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Autores principales: Yamasaki, Ryo, Lu, Haiyan, Butovsky, Oleg, Ohno, Nobuhiko, Rietsch, Anna M., Cialic, Ron, Wu, Pauline M., Doykan, Camille E., Lin, Jessica, Cotleur, Anne C., Kidd, Grahame, Zorlu, Musab M., Sun, Nathan, Hu, Weiwei, Liu, LiPing, Lee, Jar-Chi, Taylor, Sarah E., Uehlein, Lindsey, Dixon, Debra, Gu, Jinyu, Floruta, Crina M., Zhu, Min, Charo, Israel F., Weiner, Howard L., Ransohoff, Richard M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4113947/
https://www.ncbi.nlm.nih.gov/pubmed/25002752
http://dx.doi.org/10.1084/jem.20132477
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author Yamasaki, Ryo
Lu, Haiyan
Butovsky, Oleg
Ohno, Nobuhiko
Rietsch, Anna M.
Cialic, Ron
Wu, Pauline M.
Doykan, Camille E.
Lin, Jessica
Cotleur, Anne C.
Kidd, Grahame
Zorlu, Musab M.
Sun, Nathan
Hu, Weiwei
Liu, LiPing
Lee, Jar-Chi
Taylor, Sarah E.
Uehlein, Lindsey
Dixon, Debra
Gu, Jinyu
Floruta, Crina M.
Zhu, Min
Charo, Israel F.
Weiner, Howard L.
Ransohoff, Richard M.
author_facet Yamasaki, Ryo
Lu, Haiyan
Butovsky, Oleg
Ohno, Nobuhiko
Rietsch, Anna M.
Cialic, Ron
Wu, Pauline M.
Doykan, Camille E.
Lin, Jessica
Cotleur, Anne C.
Kidd, Grahame
Zorlu, Musab M.
Sun, Nathan
Hu, Weiwei
Liu, LiPing
Lee, Jar-Chi
Taylor, Sarah E.
Uehlein, Lindsey
Dixon, Debra
Gu, Jinyu
Floruta, Crina M.
Zhu, Min
Charo, Israel F.
Weiner, Howard L.
Ransohoff, Richard M.
author_sort Yamasaki, Ryo
collection PubMed
description In the human disorder multiple sclerosis (MS) and in the model experimental autoimmune encephalomyelitis (EAE), macrophages predominate in demyelinated areas and their numbers correlate to tissue damage. Macrophages may be derived from infiltrating monocytes or resident microglia, yet are indistinguishable by light microscopy and surface phenotype. It is axiomatic that T cell–mediated macrophage activation is critical for inflammatory demyelination in EAE, yet the precise details by which tissue injury takes place remain poorly understood. In the present study, we addressed the cellular basis of autoimmune demyelination by discriminating microglial versus monocyte origins of effector macrophages. Using serial block-face scanning electron microscopy (SBF-SEM), we show that monocyte-derived macrophages associate with nodes of Ranvier and initiate demyelination, whereas microglia appear to clear debris. Gene expression profiles confirm that monocyte-derived macrophages are highly phagocytic and inflammatory, whereas those arising from microglia demonstrate an unexpected signature of globally suppressed cellular metabolism at disease onset. Distinguishing tissue-resident macrophages from infiltrating monocytes will point toward new strategies to treat disease and promote repair in diverse inflammatory pathologies in varied organs.
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spelling pubmed-41139472015-01-28 Differential roles of microglia and monocytes in the inflamed central nervous system Yamasaki, Ryo Lu, Haiyan Butovsky, Oleg Ohno, Nobuhiko Rietsch, Anna M. Cialic, Ron Wu, Pauline M. Doykan, Camille E. Lin, Jessica Cotleur, Anne C. Kidd, Grahame Zorlu, Musab M. Sun, Nathan Hu, Weiwei Liu, LiPing Lee, Jar-Chi Taylor, Sarah E. Uehlein, Lindsey Dixon, Debra Gu, Jinyu Floruta, Crina M. Zhu, Min Charo, Israel F. Weiner, Howard L. Ransohoff, Richard M. J Exp Med Article In the human disorder multiple sclerosis (MS) and in the model experimental autoimmune encephalomyelitis (EAE), macrophages predominate in demyelinated areas and their numbers correlate to tissue damage. Macrophages may be derived from infiltrating monocytes or resident microglia, yet are indistinguishable by light microscopy and surface phenotype. It is axiomatic that T cell–mediated macrophage activation is critical for inflammatory demyelination in EAE, yet the precise details by which tissue injury takes place remain poorly understood. In the present study, we addressed the cellular basis of autoimmune demyelination by discriminating microglial versus monocyte origins of effector macrophages. Using serial block-face scanning electron microscopy (SBF-SEM), we show that monocyte-derived macrophages associate with nodes of Ranvier and initiate demyelination, whereas microglia appear to clear debris. Gene expression profiles confirm that monocyte-derived macrophages are highly phagocytic and inflammatory, whereas those arising from microglia demonstrate an unexpected signature of globally suppressed cellular metabolism at disease onset. Distinguishing tissue-resident macrophages from infiltrating monocytes will point toward new strategies to treat disease and promote repair in diverse inflammatory pathologies in varied organs. The Rockefeller University Press 2014-07-28 /pmc/articles/PMC4113947/ /pubmed/25002752 http://dx.doi.org/10.1084/jem.20132477 Text en © 2014 Yamsaki et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
Yamasaki, Ryo
Lu, Haiyan
Butovsky, Oleg
Ohno, Nobuhiko
Rietsch, Anna M.
Cialic, Ron
Wu, Pauline M.
Doykan, Camille E.
Lin, Jessica
Cotleur, Anne C.
Kidd, Grahame
Zorlu, Musab M.
Sun, Nathan
Hu, Weiwei
Liu, LiPing
Lee, Jar-Chi
Taylor, Sarah E.
Uehlein, Lindsey
Dixon, Debra
Gu, Jinyu
Floruta, Crina M.
Zhu, Min
Charo, Israel F.
Weiner, Howard L.
Ransohoff, Richard M.
Differential roles of microglia and monocytes in the inflamed central nervous system
title Differential roles of microglia and monocytes in the inflamed central nervous system
title_full Differential roles of microglia and monocytes in the inflamed central nervous system
title_fullStr Differential roles of microglia and monocytes in the inflamed central nervous system
title_full_unstemmed Differential roles of microglia and monocytes in the inflamed central nervous system
title_short Differential roles of microglia and monocytes in the inflamed central nervous system
title_sort differential roles of microglia and monocytes in the inflamed central nervous system
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4113947/
https://www.ncbi.nlm.nih.gov/pubmed/25002752
http://dx.doi.org/10.1084/jem.20132477
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