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

Neta Rosenzweig, Raz Dvir-Szternfeld, Afroditi Tsitsou-Kampeli, Hadas Keren-Shaul, Hila Ben-Yehuda, Pierre Weill-Raynal, Liora Cahalon, Alex Kertser, Kuti Baruch, Ido Amit, Assaf Weiner and Michal Schwartz ()
Additional contact information
Neta Rosenzweig: Weizmann Institute of Science
Raz Dvir-Szternfeld: Weizmann Institute of Science
Afroditi Tsitsou-Kampeli: Weizmann Institute of Science
Hadas Keren-Shaul: Weizmann Institute of Science
Hila Ben-Yehuda: Weizmann Institute of Science
Pierre Weill-Raynal: Weizmann Institute of Science
Liora Cahalon: Weizmann Institute of Science
Alex Kertser: Weizmann Institute of Science
Kuti Baruch: Weizmann Institute of Science
Ido Amit: Weizmann Institute of Science
Assaf Weiner: Weizmann Institute of Science
Michal Schwartz: Weizmann Institute of Science

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: 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.

Date: 2019
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41467-019-08352-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08352-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-08352-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().