CNTF-STAT3-IL-6 Axis Mediates Neuroinflammatory Cascade across Schwann Cell-Neuron-Microglia.

Zhongsheng Hu, Nan Deng, Kaili Liu, Nan Zhou, Yue Sun, Wenwen Zeng

Cell reports 2020 May 19

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Neuroinflammation is a crucial mechanism in many neurological disorders. Injury to the peripheral sensory nerves leads to a neuroinflammatory response in the somatosensory pathway, from dorsal root ganglia (DRG) to the spinal cord, contributing to neuropathic pain. How the immune reaction is initiated peripherally and propagated to the spinal cord remains less clear. Here, we find that ciliary neurotrophic factor (CNTF), highly expressed in Schwann cells, mediates neuroinflammatory response through the activating signal transducer and activator of transcription 3 (STAT3) and inducing interleukin 6 (IL-6) in sensory neurons. Cntf deficiency attenuates neuroinflammation in DRG and the spinal cord with alleviated pain post-injury. Recombinant CNTF applied to the sensory nerves recapitulates neuroinflammation in the DRG and spinal cord, with consequent pain development. We delineate the CNTF-STAT3-IL-6 axis in mediating the onset and progression of the inflammatory cascade from the periphery to the spinal cord with therapeutic implications for neuropathic pain. Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

Zhongsheng Hu, Nan Deng, Kaili Liu, Nan Zhou, Yue Sun, Wenwen Zeng. CNTF-STAT3-IL-6 Axis Mediates Neuroinflammatory Cascade across Schwann Cell-Neuron-Microglia. Cell reports. 2020 May 19;31(7):107657