Home > Publications Database > Microglial PD-1 stimulation by astrocytic PD-L1 suppresses neuroinflammation and Alzheimer's disease pathology. > print

001     163394
005     20241203165108.0
024 7 _ |a 10.15252/embj.2021108662
|2 doi
024 7 _ |a pmid:34825707
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024 7 _ |a pmc:PMC8672180
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024 7 _ |a 0261-4189
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024 7 _ |a 1460-2075
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024 7 _ |a altmetric:117673043
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037 _ _ |a DZNE-2022-00156
041 _ _ |a English
082 _ _ |a 570
100 1 _ |a Kummer, Markus P.
|0 P:(DE-2719)9000174
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245 _ _ |a Microglial PD-1 stimulation by astrocytic PD-L1 suppresses neuroinflammation and Alzheimer's disease pathology.
260 _ _ |a Hoboken, NJ [u.a.]
|c 2021
|b Wiley
336 7 _ |a article
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336 7 _ |a ARTICLE
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520 _ _ |a Chronic neuroinflammation is a pathogenic component of Alzheimer's disease (AD) that may limit the ability of the brain to clear amyloid deposits and cellular debris. Tight control of the immune system is therefore key to sustain the ability of the brain to repair itself during homeostasis and disease. The immune-cell checkpoint receptor/ligand pair PD-1/PD-L1, known for their inhibitory immune function, is expressed also in the brain. Here, we report upregulated expression of PD-L1 and PD-1 in astrocytes and microglia, respectively, surrounding amyloid plaques in AD patients and in the APP/PS1 AD mouse model. We observed juxtamembrane shedding of PD-L1 from astrocytes, which may mediate ectodomain signaling to PD-1-expressing microglia. Deletion of microglial PD-1 evoked an inflammatory response and compromised amyloid-β peptide (Aβ) uptake. APP/PS1 mice deficient for PD-1 exhibited increased deposition of Aβ, reduced microglial Aβ uptake, and decreased expression of the Aβ receptor CD36 on microglia. Therefore, ineffective immune regulation by the PD-1/PD-L1 axis contributes to Aβ plaque deposition during chronic neuroinflammation in AD.
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650 _ 7 |a APP
|2 Other
650 _ 7 |a PD-1 knockout mice
|2 Other
650 _ 7 |a PS1 mice
|2 Other
650 _ 7 |a innate immune system
|2 Other
650 _ 7 |a microglia
|2 Other
650 _ 7 |a APP protein, human
|2 NLM Chemicals
650 _ 7 |a Amyloid beta-Protein Precursor
|2 NLM Chemicals
650 _ 7 |a B7-H1 Antigen
|2 NLM Chemicals
650 _ 7 |a CD274 protein, human
|2 NLM Chemicals
650 _ 7 |a CD36 Antigens
|2 NLM Chemicals
650 _ 7 |a CD36 protein, human
|2 NLM Chemicals
650 _ 7 |a PDCD1 protein, human
|2 NLM Chemicals
650 _ 7 |a Programmed Cell Death 1 Receptor
|2 NLM Chemicals
650 _ 2 |a Aged
|2 MeSH
650 _ 2 |a Aged, 80 and over
|2 MeSH
650 _ 2 |a Alzheimer Disease: genetics
|2 MeSH
650 _ 2 |a Alzheimer Disease: immunology
|2 MeSH
650 _ 2 |a Amyloid beta-Protein Precursor: genetics
|2 MeSH
650 _ 2 |a Amyloid beta-Protein Precursor: toxicity
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Astrocytes: metabolism
|2 MeSH
650 _ 2 |a B7-H1 Antigen: metabolism
|2 MeSH
650 _ 2 |a CD36 Antigens: metabolism
|2 MeSH
650 _ 2 |a Case-Control Studies
|2 MeSH
650 _ 2 |a Disease Models, Animal
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Gene Deletion
|2 MeSH
650 _ 2 |a HEK293 Cells
|2 MeSH
650 _ 2 |a HeLa Cells
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Mice, Transgenic
|2 MeSH
650 _ 2 |a Microglia: metabolism
|2 MeSH
650 _ 2 |a Middle Aged
|2 MeSH
650 _ 2 |a Programmed Cell Death 1 Receptor: genetics
|2 MeSH
650 _ 2 |a Programmed Cell Death 1 Receptor: metabolism
|2 MeSH
650 _ 2 |a Up-Regulation
|2 MeSH
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700 1 _ |a Griep, Angelika
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700 1 _ |a Schwartz, Stephanie
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700 1 _ |a Halle, Annett
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700 1 _ |a Händler, Kristian
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700 1 _ |a Schultze, Joachim L
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700 1 _ |a Beyer, Marc-Daniel
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700 1 _ |a Latz, Eicke
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700 1 _ |a Heneka, Michael
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773 _ _ |a 10.15252/embj.2021108662
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856 4 _ |u https://pub.dzne.de/record/163394/files/DZNE-2022-00156.pdf
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