Abstract
The understanding of the dialogue between the brain and the immune system has undergone dramatic changes over the last two decades, with immense impact on the perception of neurodegenerative diseases, mental dysfunction, and many other brain pathologic conditions. Accumulated results have suggested that optimal function of the brain is dependent on support from the immune system, provided that this immune response is tightly controlled. Moreover, in contrast to the previous prevailing dogma, it is now widely accepted that circulating immune cells are needed for coping with brain pathologies and that their optimal effect is dependent on their type, location, and activity. In this perspective, we describe our own scientific journey, reviewing the milestones in attaining this understanding of the brain–immune axis integrated with numerous related studies by others. We then explain their significance in demonstrating the possibility of harnessing the immune system in a well-controlled manner for the treatment of neurodegenerative diseases.
Footnotes
This work was supported by Advanced European Research Council Grant 232835, Israel Science Foundation (ISF) Research Grant 991/16, and ISF Legacy Heritage Biomedical Science Partnership Research Grant 1354/15. We thank the Adelis and Thompson foundations for generous support of our Alzheimer's disease research.
Abbreviations used in this article:
- AD
- Alzheimer's disease
- BCSFB
- blood–cerebrospinal fluid barrier
- CP
- choroid plexus
- TREM2
- triggering receptor expressed on myeloid cells 2.
- Received July 18, 2019.
- Accepted November 18, 2019.
- Copyright © 2020 by The American Association of Immunologists, Inc.
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