Microglial immune checkpoint mechanisms

  • Nature Neurosciencevolume 21pages779786 (2018)
  • doi:10.1038/s41593-018-0145-x
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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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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).

Author information


  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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The authors declare no competing financial interests.

Corresponding author

Correspondence to Michal Schwartz.