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Microglial immune checkpoint mechanisms

Nature Neuroscience volume 21, pages 779–786 (2018)Cite this article

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An Author Correction to this article was published on 25 June 2018

This article has been updated

Abstract

Microglia differentiate from progenitors that infiltrate the nascent CNS during early embryonic development. They then remain in this unique immune-privileged environment throughout life. Multiple immune mechanisms, which we collectively refer to as microglial checkpoints, ensure efficient and tightly regulated microglial responses to perturbations in the CNS milieu. Such mechanisms are essential for proper CNS development and optimal physiological function. However, in chronic disease or aging, when a robust immune response is required, such checkpoint mechanisms may limit the ability of microglia to protect the CNS. Here we survey microglial checkpoint mechanisms and their roles in controlling microglial function throughout life and in disease, and discuss how they may be targeted therapeutically.

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Fig. 1: Microglial checkpoint mechanisms.
Fig. 2: Homeostatic microglial functions are orchestrated by checkpoint mechanisms throughout life.
Fig. 3: Microglial activators in pathology.

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  • 25 June 2018

    In the version of this article initially published, the annotation accompanying ref. 47 ended with “though the modulation of microglia.” The first word of this phrase should have been “through.” The error has been corrected in the HTML and PDF versions of the article.

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Acknowledgements

We thank S. Schwarzbaum for editing the manuscript and G. Brodsky for figure artwork. I.A. is supported by the Chan Zuckerberg Initiative (CZI), an HHMI International Scholar award, European Research Council Consolidator Grant (ERC-COG) 724471-HemTree2.0, an MRA Established Investigator Award (509044), the Israel Science Foundation (703/15), the Ernest and Bonnie Beutler Research Program of Excellence in Genomic Medicine, a Helen and Martin Kimmel award for innovative investigation, a Minerva Stiftung research grant, the Israeli Ministry of Science, Technology, and Space, the David and Fela Shapell Family Foundation, a NeuroMac DFG/Transregional Collaborative Research Center Grant, and the Abramson Family Center for Young Scientists. M.S. is supported by the Advanced European Research Council (ERC-2016-ADG 741744), the Israel Science Foundation-Legacy Heritage Biomedical Science Partnership-research (grant 1354/15), Israel Science Foundation (grant 991/16), Consolidated Anti-Aging Foundation Chicago (2016-2017) and Adelis Foundation (2018-2021).

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  1. Department of Immunology, Weizmann Institute of Science, Rehovot, Israel

    Aleksandra Deczkowska & Ido Amit

  2. Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel

    Michal Schwartz

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Deczkowska, A., Amit, I. & Schwartz, M. Microglial immune checkpoint mechanisms. Nat Neurosci 21, 779–786 (2018). https://doi.org/10.1038/s41593-018-0145-x

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