Systemic administration of PD-L1 blocking antibodies leads to removal of senescent microglia

Androsova, Y., Kertser, A., Partney, H., Nathansohn, B., Ibraheem, A., Abellanas, M. A., Croese, T., Salame, T. M., Akiva, H., Krizhanovsky, V., Schwartz, M.

Weizmann Institute of ScienceWeizmann Institute of Science · biorxiv

Paper

Abstract

Senescent microglia develop during aging and Alzheimer disease (AD), driving chronic neuroinflammation. Here we hypothesized that the previously observed disease-modifying effects of PD-1/PD-L1 blockade occur through clearance of senescent microglia. Using CyTOF, we found that a single systemic anti-PD-L1 injection leads to rapid elimination of senescent microglia in 5xFAD and aged wild-type mice, independently of Fc effector function, while increasing homeostatic microglia. These findings suggest that immune rejuvenation via PD-L1 blockade promotes disease modification in AD through senescent-microglial elimination.

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Research summary

Systemic administration of PD-L1 blocking antibodies leads to the elimination of senescent microglia, suggesting a potential mechanism for immune rejuvenation in aging-related neurodegeneration. The paper addresses the clearance of senescent cells, which is a key aspect of aging and longevity research, particularly in the context of neuroinflammation and Alzheimer's disease.

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