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PD-L1 inhibits acute and chronic pain by suppressing nociceptive neuron activity via PD-1
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 NATURE AMERICA 2017 NATURE NEUROSCIENCE Vol.20 No.7
<P>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.</P>
Multiparadigm Knowledge Programming Language LOOF
Kuan, Huang Hou,Gang, Hao Ji,Feng, Gao,Qi, Wang Zhao 대한전자공학회 1992 HICEC:Harbin International Conference on Electroni Vol.1 No.1
The paper analyses and combines logic, function and object-oriented programming paradigms, presents a new multiparadigm knowledge programming language LOOF. The language synthesizes advantages of the former three paradigms, has clear representation, strong inference and efficient computation ability. It is capable of solving complex and synthetic problems with high quality and efficiency that any single paradigm can not have.