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Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Nat+Neurosci 2017 ; 20 (7): 917-26 Nephropedia Template TP
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PD-L1 inhibits acute and chronic pain by suppressing nociceptive neuron activity via PD-1 #MMPMID28530662
Chen G; Kim YH; Li H; Luo H; Liu DL; Zhang ZJ; Lay M; Chang W; Zhang YQ; Ji RR
Nat Neurosci 2017[Jul]; 20 (7): 917-26 PMID28530662show ga
Programmed cell death ligand-1 (PD-L1) is typically produced by cancer cells and suppresses immunity through PD-1 receptor expressed on T cells. However, the role of PD-L1/PD-1 in regulating pain and neuronal function is unclear. Here we report that both melanoma and normal neural tissues including dorsal root ganglia (DRG) produce PD-L1 that can potently inhibit acute and chronic pain. Intraplantar injection of PD-L1 evokes analgesia in naïve mice via PD-1, whereas PD-L1 neutralization or PD-1 blockade induces mechanical allodynia. Mice lacking Pd1 exhibit thermal and mechanical hypersensitivity. PD-1 activation in DRG nociceptive neurons by PD-L1 induces SHP-1 phosphorylation, inhibits sodium channels, and causes hyperpolarization through activation of TREK2 K+ channels. PD-L1 also potently suppresses nociceptive neuron excitability of human DRGs. Remarkably, blocking PD-L1 or PD-1 elicits 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.