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Nat Commun. 2019 Jan 28;10(1):465. doi: 10.1038/s41467-019-08352-5.

PD-1/PD-L1 checkpoint blockade harnesses monocyte-derived macrophages to combat cognitive impairment in a tauopathy mouse model.

Author information

1
Department of Neurobiology, Weizmann Institute of Science, Rehovot, 7610001, Israel.
2
Department of Immunology, Weizmann Institute of Science, Rehovot, 7610001, Israel.
3
Department of Neurobiology, Weizmann Institute of Science, Rehovot, 7610001, Israel. Michal.Schwartz@weizmann.ac.il.

Abstract

Alzheimer's disease (AD) is a heterogeneous disorder with multiple etiologies. Harnessing the immune system by blocking the programmed cell death receptor (PD)-1 pathway in an amyloid beta mouse model was shown to evoke a sequence of immune responses that lead to disease modification. Here, blocking PD-L1, a PD-1 ligand, was found to have similar efficacy to that of PD-1 blocking in disease modification, in both animal models of AD and of tauopathy. Targeting PD-L1 in a tau-driven disease model resulted in increased immunomodulatory monocyte-derived macrophages within the brain parenchyma. Single cell RNA-seq revealed that the homing macrophages expressed unique scavenger molecules including macrophage scavenger receptor 1 (MSR1), which was shown here to be required for the effect of PD-L1 blockade in disease modification. Overall, our results demonstrate that immune checkpoint blockade targeting the PD-1/PD-L1 pathway leads to modification of common factors that go awry in AD and dementia, and thus can potentially provide an immunotherapy to help combat these diseases.

PMID:
30692527
PMCID:
PMC6349941
DOI:
10.1038/s41467-019-08352-5
[Indexed for MEDLINE]
Free PMC Article

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