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

Ryo Yamasaki, Haiyan Lu, Oleg Butovsky, Nobuhiko Ohno, Anna M. Rietsch, Ron Cialic, Pauline M. Wu, Camille E. Doykan, Jessica Lin, Anne C. Cotleur, Grahame Kidd, Musab M. Zorlu, Nathan Sun, Weiwei Hu, Li Ping Liu, Jar Chi Lee, Sarah E. Taylor, Lindsey Uehlein, Debra Dixon, Jinyu GuCrina M. Floruta, Min Zhu, Israel F. Charo, Howard L. Weiner, Richard M. Ransohoff

Research output: Contribution to journalArticle

418 Citations (Scopus)

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 monocytederived 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.

Original languageEnglish
Pages (from-to)1533-1549
Number of pages17
JournalJournal of Experimental Medicine
Volume211
Issue number8
DOIs
Publication statusPublished - 2014

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    Yamasaki, R., Lu, H., Butovsky, O., Ohno, N., Rietsch, A. M., Cialic, R., Wu, P. M., Doykan, C. E., Lin, J., Cotleur, A. C., Kidd, G., Zorlu, M. M., Sun, N., Hu, W., Liu, L. P., Lee, J. C., Taylor, S. E., Uehlein, L., Dixon, D., ... Ransohoff, R. M. (2014). Differential roles of microglia and monocytes in the inflamed central nervous system. Journal of Experimental Medicine, 211(8), 1533-1549. https://doi.org/10.1084/jem.20132477