Microglial PD‐1 stimulation by astrocytic PD‐L1 suppresses neuroinflammation and Alzheimer’s disease pathology

  • Kummer M
  • Ising C
  • Kummer C
  • et al.
59Citations
Citations of this article
92Readers
Mendeley users who have this article in their library.

Abstract

Chronic neuroinflammation is a pathogenic component of Alzhei-mer'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 micro-glia, 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 ectodo-main signaling to PD-1-expressing microglia. Deletion of microglial PD-1 evoked an inflammatory response and compromised amyloid-b peptide (Ab) uptake. APP/PS1 mice deficient for PD-1 exhibited increased deposition of Ab, reduced microglial Ab uptake, and decreased expression of the Ab receptor CD36 on microglia. Therefore , ineffective immune regulation by the PD-1/PD-L1 axis contributes to Ab plaque deposition during chronic neuroinflammation in AD.

Cite

CITATION STYLE

APA

Kummer, M. P., Ising, C., Kummer, C., Sarlus, H., Griep, A., Vieira‐Saecker, A., … Heneka, M. T. (2021). Microglial PD‐1 stimulation by astrocytic PD‐L1 suppresses neuroinflammation and Alzheimer’s disease pathology. The EMBO Journal, 40(24). https://doi.org/10.15252/embj.2021108662

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free