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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

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, Michal Schwartz

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. More... »

PAGES

465

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    http://scigraph.springernature.com/pub.10.1038/s41467-019-08352-5

    DOI

    http://dx.doi.org/10.1038/s41467-019-08352-5

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1111676451

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30692527


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