Differential roles of microglia and monocytes in the inflamed central nervous system
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Author
Yamasaki, Ryo
Lu, Haiyan
Ohno, Nobuhiko
Rietsch, Anna M.
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.
Ransohoff, Richard M.
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1084/jem.20132477Metadata
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Yamasaki, R., H. Lu, O. Butovsky, N. Ohno, A. M. Rietsch, R. Cialic, P. M. Wu, et al. 2014. “Differential roles of microglia and monocytes in the inflamed central nervous system.” The Journal of Experimental Medicine 211 (8): 1533-1549. doi:10.1084/jem.20132477. http://dx.doi.org/10.1084/jem.20132477.Abstract
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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4113947/pdf/Terms of Use
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http://nrs.harvard.edu/urn-3:HUL.InstRepos:13890739
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