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000163394 0247_ $$2doi$$a10.15252/embj.2021108662
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000163394 0247_ $$2pmc$$apmc:PMC8672180
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000163394 0247_ $$2ISSN$$a1460-2075
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000163394 037__ $$aDZNE-2022-00156
000163394 041__ $$aEnglish
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000163394 1001_ $$0P:(DE-2719)9000174$$aKummer, Markus P.$$b0$$udzne
000163394 245__ $$aMicroglial PD-1 stimulation by astrocytic PD-L1 suppresses neuroinflammation and Alzheimer's disease pathology.
000163394 260__ $$aHoboken, NJ [u.a.]$$bWiley$$c2021
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000163394 520__ $$aChronic neuroinflammation is a pathogenic component of Alzheimer's disease (AD) that may limit the ability of the brain to clear amyloid deposits and cellular debris. Tight control of the immune system is therefore key to sustain the ability of the brain to repair itself during homeostasis and disease. The immune-cell checkpoint receptor/ligand pair PD-1/PD-L1, known for their inhibitory immune function, is expressed also in the brain. Here, we report upregulated expression of PD-L1 and PD-1 in astrocytes and microglia, respectively, surrounding amyloid plaques in AD patients and in the APP/PS1 AD mouse model. We observed juxtamembrane shedding of PD-L1 from astrocytes, which may mediate ectodomain signaling to PD-1-expressing microglia. Deletion of microglial PD-1 evoked an inflammatory response and compromised amyloid-β peptide (Aβ) uptake. APP/PS1 mice deficient for PD-1 exhibited increased deposition of Aβ, reduced microglial Aβ uptake, and decreased expression of the Aβ receptor CD36 on microglia. Therefore, ineffective immune regulation by the PD-1/PD-L1 axis contributes to Aβ plaque deposition during chronic neuroinflammation in AD.
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000163394 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x1
000163394 536__ $$0G:(DE-HGF)POF4-351$$a351 - Brain Function (POF4-351)$$cPOF4-351$$fPOF IV$$x2
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000163394 650_7 $$2Other$$aAPP
000163394 650_7 $$2Other$$aPD-1 knockout mice
000163394 650_7 $$2Other$$aPS1 mice
000163394 650_7 $$2Other$$ainnate immune system
000163394 650_7 $$2Other$$amicroglia
000163394 650_7 $$2NLM Chemicals$$aAPP protein, human
000163394 650_7 $$2NLM Chemicals$$aAmyloid beta-Protein Precursor
000163394 650_7 $$2NLM Chemicals$$aB7-H1 Antigen
000163394 650_7 $$2NLM Chemicals$$aCD274 protein, human
000163394 650_7 $$2NLM Chemicals$$aCD36 Antigens
000163394 650_7 $$2NLM Chemicals$$aCD36 protein, human
000163394 650_7 $$2NLM Chemicals$$aPDCD1 protein, human
000163394 650_7 $$2NLM Chemicals$$aProgrammed Cell Death 1 Receptor
000163394 650_2 $$2MeSH$$aAged
000163394 650_2 $$2MeSH$$aAged, 80 and over
000163394 650_2 $$2MeSH$$aAlzheimer Disease: genetics
000163394 650_2 $$2MeSH$$aAlzheimer Disease: immunology
000163394 650_2 $$2MeSH$$aAmyloid beta-Protein Precursor: genetics
000163394 650_2 $$2MeSH$$aAmyloid beta-Protein Precursor: toxicity
000163394 650_2 $$2MeSH$$aAnimals
000163394 650_2 $$2MeSH$$aAstrocytes: metabolism
000163394 650_2 $$2MeSH$$aB7-H1 Antigen: metabolism
000163394 650_2 $$2MeSH$$aCD36 Antigens: metabolism
000163394 650_2 $$2MeSH$$aCase-Control Studies
000163394 650_2 $$2MeSH$$aDisease Models, Animal
000163394 650_2 $$2MeSH$$aFemale
000163394 650_2 $$2MeSH$$aGene Deletion
000163394 650_2 $$2MeSH$$aHEK293 Cells
000163394 650_2 $$2MeSH$$aHeLa Cells
000163394 650_2 $$2MeSH$$aHumans
000163394 650_2 $$2MeSH$$aMale
000163394 650_2 $$2MeSH$$aMice
000163394 650_2 $$2MeSH$$aMice, Transgenic
000163394 650_2 $$2MeSH$$aMicroglia: metabolism
000163394 650_2 $$2MeSH$$aMiddle Aged
000163394 650_2 $$2MeSH$$aProgrammed Cell Death 1 Receptor: genetics
000163394 650_2 $$2MeSH$$aProgrammed Cell Death 1 Receptor: metabolism
000163394 650_2 $$2MeSH$$aUp-Regulation
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000163394 7001_ $$0P:(DE-2719)2812463$$aIsing, Christina$$b1$$udzne
000163394 7001_ $$aKummer, Christiane$$b2
000163394 7001_ $$0P:(DE-2719)2811644$$aSarlus, Heela$$b3$$udzne
000163394 7001_ $$0P:(DE-2719)2811029$$aGriep, Angelika$$b4$$udzne
000163394 7001_ $$0P:(DE-2719)9000382$$aVieira-Saecker, Ana$$b5$$udzne
000163394 7001_ $$0P:(DE-2719)9000454$$aSchwartz, Stephanie$$b6$$udzne
000163394 7001_ $$0P:(DE-2719)2812038$$aHalle, Annett$$b7$$udzne
000163394 7001_ $$0P:(DE-2719)2813026$$aBrückner, Matthias$$b8$$udzne
000163394 7001_ $$0P:(DE-2719)2812735$$aHändler, Kristian$$b9$$udzne
000163394 7001_ $$0P:(DE-2719)2811660$$aSchultze, Joachim L$$b10$$udzne
000163394 7001_ $$0P:(DE-2719)2812219$$aBeyer, Marc-Daniel$$b11$$udzne
000163394 7001_ $$0P:(DE-2719)2000062$$aLatz, Eicke$$b12$$udzne
000163394 7001_ $$0P:(DE-2719)2000008$$aHeneka, Michael$$b13$$eLast author$$udzne
000163394 773__ $$0PERI:(DE-600)1467419-1$$a10.15252/embj.2021108662$$gVol. 40, no. 24$$n24$$pe108662$$tThe EMBO journal$$v40$$x1460-2075$$y2021
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