The brain-immune ecosystem: A transformed understanding of brain immunity and immunotherapy to defeat brain diseases
Since the studies of Medawar and Burnet some 70 years ago, it was widely accepted that the CNS cannot tolerate any immune activity, under any circumstances. Over the past two decades, my team initiated a reversal of this dogma, by demonstrating that the brain requires support from innate and adaptiv...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-04-01
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| Series: | Journal of Affective Disorders Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S266691532300104X |
| _version_ | 1797854493045424128 |
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| author | Michal Schwartz |
| author_facet | Michal Schwartz |
| author_sort | Michal Schwartz |
| collection | DOAJ |
| description | Since the studies of Medawar and Burnet some 70 years ago, it was widely accepted that the CNS cannot tolerate any immune activity, under any circumstances. Over the past two decades, my team initiated a reversal of this dogma, by demonstrating that the brain requires support from innate and adaptive immune cells for its maintenance and repair. Deep understanding of these relationships by our team and by others led us to propose that the immune cells that are hosted within the brain's borders, together with neurons and non-neuronal cells, form an ecosystem that enhances the resilience of the brain and its robustness in withstanding continuous and diverse perturbations. Accordingly, any dysfunction in this brain-immune communication might impact brain activity. As aging is the major risk factor in dementia including Alzheimer's disease, we propose that dysfunction of any aspect of the brain-immune ecosystem could affect disease onset and severity, but may be amenable to immune intervention. This model led us to propose that defeating such diseases might be accomplished by harnessing the immune system, which is either exhausted or insufficient. We found that rejuvenating the immune system by transiently blocking the inhibitory PD-1/PD-L1 immune checkpoint pathway, initiates an immune response in the periphery that leads to disease modification within the brain by reducing multiple parameters that contribute to disease escalation, including neural loss, local inflammation, and phospho- and aggregated-tau in tauopathy, and soluble oligomers of amyloid beta in amyloidosis. In this lecture, we will focus on the choroid plexus-immune-brain axis as a gateway for leukocyte homing to the brain and as a site that remotely affects the brain's fate, via the CSF. Together, our studies show that targeting the immune system provides new avenues for understanding and treating neurodegenerative diseases. |
| first_indexed | 2024-04-09T20:08:02Z |
| format | Article |
| id | doaj.art-d253978509e64b10828a5248ba517c5b |
| institution | Directory Open Access Journal |
| issn | 2666-9153 |
| language | English |
| last_indexed | 2024-04-09T20:08:02Z |
| publishDate | 2023-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Affective Disorders Reports |
| spelling | doaj.art-d253978509e64b10828a5248ba517c5b2023-04-01T08:52:03ZengElsevierJournal of Affective Disorders Reports2666-91532023-04-0112100565The brain-immune ecosystem: A transformed understanding of brain immunity and immunotherapy to defeat brain diseasesMichal Schwartz0Weizmann Institute of Science, Rehovot, IsraelSince the studies of Medawar and Burnet some 70 years ago, it was widely accepted that the CNS cannot tolerate any immune activity, under any circumstances. Over the past two decades, my team initiated a reversal of this dogma, by demonstrating that the brain requires support from innate and adaptive immune cells for its maintenance and repair. Deep understanding of these relationships by our team and by others led us to propose that the immune cells that are hosted within the brain's borders, together with neurons and non-neuronal cells, form an ecosystem that enhances the resilience of the brain and its robustness in withstanding continuous and diverse perturbations. Accordingly, any dysfunction in this brain-immune communication might impact brain activity. As aging is the major risk factor in dementia including Alzheimer's disease, we propose that dysfunction of any aspect of the brain-immune ecosystem could affect disease onset and severity, but may be amenable to immune intervention. This model led us to propose that defeating such diseases might be accomplished by harnessing the immune system, which is either exhausted or insufficient. We found that rejuvenating the immune system by transiently blocking the inhibitory PD-1/PD-L1 immune checkpoint pathway, initiates an immune response in the periphery that leads to disease modification within the brain by reducing multiple parameters that contribute to disease escalation, including neural loss, local inflammation, and phospho- and aggregated-tau in tauopathy, and soluble oligomers of amyloid beta in amyloidosis. In this lecture, we will focus on the choroid plexus-immune-brain axis as a gateway for leukocyte homing to the brain and as a site that remotely affects the brain's fate, via the CSF. Together, our studies show that targeting the immune system provides new avenues for understanding and treating neurodegenerative diseases.http://www.sciencedirect.com/science/article/pii/S266691532300104X |
| spellingShingle | Michal Schwartz The brain-immune ecosystem: A transformed understanding of brain immunity and immunotherapy to defeat brain diseases Journal of Affective Disorders Reports |
| title | The brain-immune ecosystem: A transformed understanding of brain immunity and immunotherapy to defeat brain diseases |
| title_full | The brain-immune ecosystem: A transformed understanding of brain immunity and immunotherapy to defeat brain diseases |
| title_fullStr | The brain-immune ecosystem: A transformed understanding of brain immunity and immunotherapy to defeat brain diseases |
| title_full_unstemmed | The brain-immune ecosystem: A transformed understanding of brain immunity and immunotherapy to defeat brain diseases |
| title_short | The brain-immune ecosystem: A transformed understanding of brain immunity and immunotherapy to defeat brain diseases |
| title_sort | brain immune ecosystem a transformed understanding of brain immunity and immunotherapy to defeat brain diseases |
| url | http://www.sciencedirect.com/science/article/pii/S266691532300104X |
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