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Emerging Role of PD-1 in the Central Nervous System and Brain Diseases

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Abstract

Programmed cell death protein 1 (PD-1) is an immune checkpoint modulator and a major target of immunotherapy as anti-PD-1 monoclonal antibodies have demonstrated remarkable efficacy in cancer treatment. Accumulating evidence suggests an important role of PD-1 in the central nervous system (CNS). PD-1 has been implicated in CNS disorders such as brain tumors, Alzheimer’s disease, ischemic stroke, spinal cord injury, multiple sclerosis, cognitive function, and pain. PD-1 signaling suppresses the CNS immune response via resident microglia and infiltrating peripheral immune cells. Notably, PD-1 is also widely expressed in neurons and suppresses neuronal activity via downstream Src homology 2 domain-containing protein tyrosine phosphatase 1 and modulation of ion channel function. An improved understanding of PD-1 signaling in the cross-talk between glial cells, neurons, and peripheral immune cells in the CNS will shed light on immunomodulation, neuromodulation, and novel strategies for treating brain diseases.

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Acknowledgements

The work related to this review was partially supported by Duke University Fund.

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Authors and Affiliations

  1. Department of Anesthesiology, Duke University Medical Center, Durham, 27710, USA

    Junli Zhao, Alexus Roberts, Zilong Wang & Ru-Rong Ji

  2. Department of Biology, Duke University Medical Center, Durham, 27710, USA

    Alexus Roberts

  3. Department of Neurobiology, Duke University Medical Center, Durham, 27710, USA

    Justin Savage & Ru-Rong Ji

  4. Department of Cell Biology, Duke University Medical Center, Durham, 27710, USA

    Ru-Rong Ji

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  1. Junli Zhao
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Correspondence to Junli Zhao or Ru-Rong Ji.

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Zhao, J., Roberts, A., Wang, Z. et al. Emerging Role of PD-1 in the Central Nervous System and Brain Diseases. Neurosci. Bull. 37, 1188–1202 (2021). https://doi.org/10.1007/s12264-021-00683-y

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