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Brain Behav Immun. 2018 Oct;73:708-716. doi: 10.1016/j.bbi.2018.08.006. Epub 2018 Aug 4.

PD-1 deficiency is not sufficient to induce myeloid mobilization to the brain or alter the inflammatory profile during chronic neurodegeneration.

Author information

1
Biological Sciences, University of Southampton, United Kingdom.
2
Biological Sciences, University of Southampton, United Kingdom. Electronic address: d.gomez-nicola@soton.ac.uk.

Abstract

Innate immune activation is a major driver of neurodegenerative disease and immune regulatory pathways could be potential targets for therapeutic intervention. Recently, Programmed cell death-1 (PD-1) immune checkpoint inhibition has been proposed to mount an IFN-γ-dependent systemic immune response, leading to the recruitment of peripheral myeloid cells to the brain and neuropathological and functional improvements in mice with Alzheimer's disease-like β-amyloid pathology. Here we investigate the impact of PD-1 deficiency on murine prion disease (ME7 strain), a model of chronic neurodegeneration. Although PD-1 was found to be increased in the brain of prion mice, the absence of PD-1 did not cause myeloid cell infiltration into the brain or major changes in the inflammatory profile. However, we observed a slight exacerbation of the behavioural phenotype of ME7 mice upon PD-1 deficiency. These results do not support the possibility of using immune checkpoint blockade as a therapeutic strategy in neurodegenerative disease.

KEYWORDS:

Myeloid cells; Neuroinflammation; Prion disease; Programmed cell death-1

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