PD-L1 inhibits acute and chronic pain by suppressing nociceptive neuron activity via PD-1
- Authors
- Chen, Gang; Kim, Yong Ho; Li, Hui; Luo, Hao; Liu, Da-Lu; Zhang, Zhi-Jun; Lay, Mark; Chang, Wonseok; Zhang, Yu-Qiu; Ji, Ru-Rong
- Issue Date
- Jul-2017
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- NATURE NEUROSCIENCE, v.20, no.7, pp.917 - +
- Journal Title
- NATURE NEUROSCIENCE
- Volume
- 20
- Number
- 7
- Start Page
- 917
- End Page
- +
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/5972
- DOI
- 10.1038/nn.4571
- ISSN
- 1097-6256
- Abstract
- 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.
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