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PD-L1 inhibits acute and chronic pain by suppressing nociceptive neuron activity via PD-1.

Publication ,  Journal Article
Chen, G; Kim, YH; Li, H; Luo, H; Liu, D-L; Zhang, Z-J; Lay, M; Chang, W; Zhang, Y-Q; Ji, R-R
Published in: Nat Neurosci
July 2017

Programmed cell death ligand-1 (PD-L1) is typically produced by cancer cells and suppresses immunity through the receptor PD-1 expressed on T cells. However, the role of PD-L1 and PD-1 in regulating pain and neuronal function is unclear. Here we report that both melanoma and normal neural tissues including dorsal root ganglion (DRG) produce PD-L1 that can potently inhibit acute and chronic pain. Intraplantar injection of PD-L1 evoked analgesia in naive mice via PD-1, whereas PD-L1 neutralization or PD-1 blockade induced mechanical allodynia. Mice lacking Pd1 (Pdcd1) exhibited thermal and mechanical hypersensitivity. PD-1 activation in DRG nociceptive neurons by PD-L1 induced phosphorylation of the tyrosine phosphatase SHP-1, inhibited sodium channels and caused hyperpolarization through activation of TREK2 K+ channels. PD-L1 also potently suppressed nociceptive neuron excitability in human DRGs. Notably, blocking PD-L1 or PD-1 elicited spontaneous pain and allodynia in melanoma-bearing mice. Our findings identify a previously unrecognized role of PD-L1 as an endogenous pain inhibitor and a neuromodulator.

Duke Scholars

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Published In

Nat Neurosci

DOI

EISSN

1546-1726

Publication Date

July 2017

Volume

20

Issue

7

Start / End Page

917 / 926

Location

United States

Related Subject Headings

  • Synaptic Transmission
  • Sodium Channels
  • Rats
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Programmed Cell Death 1 Receptor
  • Primary Cell Culture
  • Potassium Channels, Tandem Pore Domain
  • Phosphorylation
  • Pain Threshold
  • Neurons
 

Citation

APA
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ICMJE
MLA
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Chen, G., Kim, Y. H., Li, H., Luo, H., Liu, D.-L., Zhang, Z.-J., … Ji, R.-R. (2017). PD-L1 inhibits acute and chronic pain by suppressing nociceptive neuron activity via PD-1. Nat Neurosci, 20(7), 917–926. https://doi.org/10.1038/nn.4571
Chen, Gang, Yong Ho Kim, Hui Li, Hao Luo, Da-Lu Liu, Zhi-Jun Zhang, Mark Lay, Wonseok Chang, Yu-Qiu Zhang, and Ru-Rong Ji. “PD-L1 inhibits acute and chronic pain by suppressing nociceptive neuron activity via PD-1.Nat Neurosci 20, no. 7 (July 2017): 917–26. https://doi.org/10.1038/nn.4571.
Chen G, Kim YH, Li H, Luo H, Liu D-L, Zhang Z-J, et al. PD-L1 inhibits acute and chronic pain by suppressing nociceptive neuron activity via PD-1. Nat Neurosci. 2017 Jul;20(7):917–26.
Chen, Gang, et al. “PD-L1 inhibits acute and chronic pain by suppressing nociceptive neuron activity via PD-1.Nat Neurosci, vol. 20, no. 7, July 2017, pp. 917–26. Pubmed, doi:10.1038/nn.4571.
Chen G, Kim YH, Li H, Luo H, Liu D-L, Zhang Z-J, Lay M, Chang W, Zhang Y-Q, Ji R-R. PD-L1 inhibits acute and chronic pain by suppressing nociceptive neuron activity via PD-1. Nat Neurosci. 2017 Jul;20(7):917–926.

Published In

Nat Neurosci

DOI

EISSN

1546-1726

Publication Date

July 2017

Volume

20

Issue

7

Start / End Page

917 / 926

Location

United States

Related Subject Headings

  • Synaptic Transmission
  • Sodium Channels
  • Rats
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Programmed Cell Death 1 Receptor
  • Primary Cell Culture
  • Potassium Channels, Tandem Pore Domain
  • Phosphorylation
  • Pain Threshold
  • Neurons