Transforming the understanding of brain immunity
Abstract
Contemporary studies have completely changed the view of brain immunity from envisioning the brain as isolated and inaccessible to peripheral immune cells to an organ in close physical and functional communication with the immune system for its maintenance, function, and repair. Circulating immune cells reside in special niches in the brain’s borders, the choroid plexus, meninges, and perivascular spaces, from which they patrol and sense the brain in a remote manner. These niches, together with the meningeal lymphatic system and skull microchannels, provide multiple routes of interaction between the brain and the immune system, in addition to the blood vasculature. In this Review, we describe current ideas about brain immunity and their implications for brain aging, diseases, and immune-based therapeutic approaches.
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The view of the brain as an immune-privileged organ has shifted towards an understanding that crosstalk between brain-resident and peripheral immune cells plays a pivotal role in physiological and pathological brain conditions.
“The old-fashioned view of the brain as an immune-privileged organ has progressively shifted towards a more nuanced understanding, in which the crosstalk between brain-resident and peripheral immune cells plays a pivotal role in both physiological and pathological brain con ditions [39].”
From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [39]
Recent studies have indicated that leukocyte infiltration and aberrant inflammation exert protective or detrimental effects on the development of neurodegenerative diseases.
“Recent studies have indicated that leukocyte infiltration and aberrant inflammation exert protective or detrimental effects on the development of neurodegenerative diseases182,183.”
From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [182]
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The WAVE complex in developmental and adulthood brain disorders
Kim, H.-G., Berdasco, C., Nairn, A. C., & Kim, Y. (2025) · Experimental & Molecular Medicine · doi:10.1038/s12276-024-01386-w · Cited by 8 · see citing works
Is there a role for B cells in Alzheimer's disease?
Charavner, E.-L., Fillatreau, S., & El Behi, M. (2026) · Cellular Immunology · doi:10.1016/j.cellimm.2026.105154
- Authors
- Castellani, G., Croese, T., Peralta Ramos, J. M., & Schwartz, M.
- Affiliations
- Weizmann Institute of Science (IL)
- Department of Brain Sciences, Weizmann Institute of Science, Rehovot, Israel.
- Corresponding author
- Castellani, Giulia
- Croese, Tommaso
- Schwartz, Michal
- Venue
- Science
- Published
- 2023-04-07
- Volume
- 380
- Issue
- 6640
- Pages
- eabo7649-eabo7649
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W4362661856
- Cited by
- 386
- References
- 49
- Citations by year
- 2026: 115 · 2025: 128 · 2024: 112 · 2023: 31
- FWCI
- 10.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Keywords
- brain immunity, neuroimmunology, choroid plexus, meninges, perivascular spaces, meningeal lymphatic system, brain aging, neuroinflammation, immunotherapy
- MeSH terms
- Animals, Brain, Cell Movement, Humans, Immune System, Lymphatic System, Meninges, Myeloid Cells
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