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Microglial PD-1 stimulation by astrocytic PD-L1 suppresses neuroinflammation and Alzheimer's disease pathology.
Kummer, Markus P; Ising, Christina; Kummer, Christiane; Sarlus, Heela; Griep, Angelika; Vieira-Saecker, Ana; Schwartz, Stephanie; Halle, Annett; Brückner, Matthias; Händler, Kristian; Schultze, Joachim L; Beyer, Marc; Latz, Eicke; Heneka, Michael T.
Afiliación
  • Kummer MP; Department of Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn Medical Faculty, Bonn, Germany.
  • Ising C; Department of Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn Medical Faculty, Bonn, Germany.
  • Kummer C; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
  • Sarlus H; Department of Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn Medical Faculty, Bonn, Germany.
  • Griep A; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
  • Vieira-Saecker A; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
  • Schwartz S; Department of Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn Medical Faculty, Bonn, Germany.
  • Halle A; Department of Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn Medical Faculty, Bonn, Germany.
  • Brückner M; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
  • Händler K; Caesar Research Center, Bonn, Germany.
  • Schultze JL; Systems Medicine, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
  • Beyer M; PRECISE Platform for Single Cell Genomics and Epigenomics, German Center for Neurodegenerative Diseases (DZNE) and University of Bonn, Bonn, Germany.
  • Latz E; Systems Medicine, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
  • Heneka MT; PRECISE Platform for Single Cell Genomics and Epigenomics, German Center for Neurodegenerative Diseases (DZNE) and University of Bonn, Bonn, Germany.
EMBO J ; 40(24): e108662, 2021 12 15.
Article en En | MEDLINE | ID: mdl-34825707
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-ß peptide (Aß) uptake. APP/PS1 mice deficient for PD-1 exhibited increased deposition of Aß, reduced microglial Aß uptake, and decreased expression of the Aß receptor CD36 on microglia. Therefore, ineffective immune regulation by the PD-1/PD-L1 axis contributes to Aß plaque deposition during chronic neuroinflammation in AD.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Regulación hacia Arriba / Precursor de Proteína beta-Amiloide / Enfermedad de Alzheimer / Antígeno B7-H1 / Receptor de Muerte Celular Programada 1 Tipo de estudio: Observational_studies Límite: Aged / Aged80 / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: EMBO J Año: 2021 Tipo del documento: Article País de afiliación: Alemania

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Regulación hacia Arriba / Precursor de Proteína beta-Amiloide / Enfermedad de Alzheimer / Antígeno B7-H1 / Receptor de Muerte Celular Programada 1 Tipo de estudio: Observational_studies Límite: Aged / Aged80 / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: EMBO J Año: 2021 Tipo del documento: Article País de afiliación: Alemania