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Title:
PD-1/PD-L1 checkpoint blockade harnesses monocyte-derived macrophages to combat cognitive impairment in a tauopathy mouse model | Nature Communications
Description:
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. Blocking the PD-1 pathway was shown to be effective in amyloid beta mouse models, yet little is known about its therapeutic potential in models of tauopathy. The authors show here that blocking PD-L1, a PD-1 ligand, is similarly effective, and that both treatments reversed cognitive deficiencies, and modified disease pathology not only in an animal model of AD, but also in the DM-hTAU mouse tauopathy model, through a mechanism that involves monocyte-derived macrophages.
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nature portfolio privacy policy anti-pd-l1-treated dm-htaugfp/+ mice open central area anti-pd-l1 blocking antibody mitigated rat-anti-mouse pd-l1 antibody editing advertising anti-pd-l1-treated 5xfad mice nature communications anti-pd-l1 igg-treated groups anti-pd-l1-treated groups relative mars-seq libraries gfp-bm-chimeric dm-htau mice anti-pd-l1 antibody treatment relative anti-pd-l1 antibodies demonstrated thermo scientific anti-pd-l1-treated animals relative anti-human pd-l1 antibody single-cell libraries targets pd-1/pd-l1 blockade dm-htau + anti-pd-l1 anti-human pd-l1 antibodies brilliant-violet 421-conjugated anti-cd45 dm-tau + anti-pd-l1 anti-pd-1/pd-l1 antibodies molecular research center single-cell rna-seq revealed human anti-pd-l1 clone additional anti-pd-l1 antibody pd-1/pd-l1 pathway leads group received anti-pd-l1 anti-mouse pd-l1 antibody anti-pd-l1 antibody resulted anti-pd-l1 antibody relative anti-pd-l1-treated mice anti-pd-1 antibody-treated group anti-pd-l1-treated groups pd-l1-blocking antibody directed current anti-pd-l1 treatment researcher reprints anti-pd-l1 antibody treatment research grant anti-pd-1-treated 5xfad mice performed single-cell rna-seq sequencing-ready library scavenger receptor-mediated adhesion pe-conjugated anti-cd3 igg2b-treated dm-htau mice
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- Can immunotherapy treat neurodegeneration?
- Does neuroinflammation drive the relationship between tau hyperphosphorylation and dementia development following traumatic brain injury?
- T cell-microglial dialogue in Parkinson’s disease and amyotrophic lateral sclerosis: are we listening?
- Who fans the flames of Alzheimer’s disease brains?
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