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

PD-1 deficiency is not sufficient to induce myeloid mobilization to the brain or alter the inflammatory profile during chronic neurodegeneration
PD-1 deficiency is not sufficient to induce myeloid mobilization to the brain or alter the inflammatory profile during chronic neurodegeneration
Chronic inflammation 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.
0889-1591
Obst, Juliane
0c499ee6-0290-4792-8c99-049e05332227
Mancuso, Renzo
05786562-a993-4e37-926e-3c1fcf50b36d
Simon, Emilie
22a3ee84-1834-4038-91cb-15d6163b1c56
Gomez-Nicola, Diego
0680aa66-9dee-47cf-a8d3-e39c988f85b5
Obst, Juliane
0c499ee6-0290-4792-8c99-049e05332227
Mancuso, Renzo
05786562-a993-4e37-926e-3c1fcf50b36d
Simon, Emilie
22a3ee84-1834-4038-91cb-15d6163b1c56
Gomez-Nicola, Diego
0680aa66-9dee-47cf-a8d3-e39c988f85b5

Obst, Juliane, Mancuso, Renzo, Simon, Emilie and Gomez-Nicola, Diego (2018) PD-1 deficiency is not sufficient to induce myeloid mobilization to the brain or alter the inflammatory profile during chronic neurodegeneration. Brain, Behavior and Immunity. (doi:10.1016/j.bbi.2018.08.006).

Record type: Article

Abstract

Chronic inflammation 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.

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Accepted/In Press date: 3 August 2018
e-pub ahead of print date: 4 August 2018

Identifiers

Local EPrints ID: 422952
URI: http://eprints.soton.ac.uk/id/eprint/422952
ISSN: 0889-1591
PURE UUID: 61a50981-c60a-42ea-8d71-dc95799a9347
ORCID for Diego Gomez-Nicola: ORCID iD orcid.org/0000-0002-5316-2682

Catalogue record

Date deposited: 08 Aug 2018 16:30
Last modified: 22 Nov 2021 02:59

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Contributors

Author: Juliane Obst
Author: Renzo Mancuso
Author: Emilie Simon

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