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PD-1 Regulates GABAergic Neurotransmission and GABA-Mediated Analgesia and Anesthesia.

Publication ,  Journal Article
Jiang, C; Wang, Z; Donnelly, CR; Wang, K; Andriessen, AS; Tao, X; Matsuda, M; Zhao, J; Ji, R-R
Published in: iScience
October 23, 2020

The immune checkpoint inhibitor programmed cell death protein 1 (PD-1) plays a critical role in immune regulation. Recent studies have demonstrated functional PD-1 expression in peripheral sensory neurons, which contributes to neuronal excitability, pain, and opioid analgesia. Here we report neuronal expression and function of PD-1 in the central nervous system (CNS), including the spinal cord, thalamus, and cerebral cortex. Notably, GABA-induced currents in spinal dorsal horn neurons, thalamic neurons, and cortical neurons are suppressed by the PD-1-neutralizing immunotherapeutic Nivolumab in spinal cord slices, brain slices, and dissociated cortical neurons. Reductions in GABA-mediated currents in CNS neurons were also observed in Pd1 -/- mice without changes in GABA receptor expression. Mechanistically, Nivolumab binds spinal cord neurons and elicits ERK phosphorylation to suppress GABA currents. Finally, both GABA-mediated analgesia and anesthesia are impaired by Pd1 deficiency. Our findings reveal PD-1 as a CNS-neuronal inhibitor that regulates GABAergic signaling and GABA-mediated behaviors.

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Published In

iScience

DOI

EISSN

2589-0042

Publication Date

October 23, 2020

Volume

23

Issue

10

Start / End Page

101570

Location

United States
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Jiang, C., Wang, Z., Donnelly, C. R., Wang, K., Andriessen, A. S., Tao, X., … Ji, R.-R. (2020). PD-1 Regulates GABAergic Neurotransmission and GABA-Mediated Analgesia and Anesthesia. IScience, 23(10), 101570. https://doi.org/10.1016/j.isci.2020.101570
Jiang, Changyu, Zilong Wang, Christopher R. Donnelly, Kaiyuan Wang, Amanda S. Andriessen, Xueshu Tao, Megumi Matsuda, Junli Zhao, and Ru-Rong Ji. “PD-1 Regulates GABAergic Neurotransmission and GABA-Mediated Analgesia and Anesthesia.IScience 23, no. 10 (October 23, 2020): 101570. https://doi.org/10.1016/j.isci.2020.101570.
Jiang C, Wang Z, Donnelly CR, Wang K, Andriessen AS, Tao X, et al. PD-1 Regulates GABAergic Neurotransmission and GABA-Mediated Analgesia and Anesthesia. iScience. 2020 Oct 23;23(10):101570.
Jiang, Changyu, et al. “PD-1 Regulates GABAergic Neurotransmission and GABA-Mediated Analgesia and Anesthesia.IScience, vol. 23, no. 10, Oct. 2020, p. 101570. Pubmed, doi:10.1016/j.isci.2020.101570.
Jiang C, Wang Z, Donnelly CR, Wang K, Andriessen AS, Tao X, Matsuda M, Zhao J, Ji R-R. PD-1 Regulates GABAergic Neurotransmission and GABA-Mediated Analgesia and Anesthesia. iScience. 2020 Oct 23;23(10):101570.
Journal cover image

Published In

iScience

DOI

EISSN

2589-0042

Publication Date

October 23, 2020

Volume

23

Issue

10

Start / End Page

101570

Location

United States