Department of Physiology, University of Kentucky, 800 Rose Street, Lexington, Kentucky, 40536-0298.
Graduate Program in Neuroscience, University of Minnesota, Minneapolis, Minnesota.
Glia. 2017 Dec;65(12):1976-1989. doi: 10.1002/glia.23208. Epub 2017 Aug 29.
The complement 3a receptor (C3aR1) participates in microglial signaling under pathological conditions and was recently shown to be activated by the neuropeptide TLQP-21. We previously demonstrated that TLQP-21 elicits hyperalgesia and contributes to nerve injury-induced hypersensitivity through an unknown mechanism in the spinal cord. Here we determined that this mechanism requires C3aR1 and that microglia are the cellular target for TLQP-21. We propose a novel neuroimmune signaling pathway involving TLQP-21-induced activation of microglial C3aR1 that then contributes to spinal neuroplasticity and neuropathic pain. This unique dual-ligand activation of C3aR1 by a neuropeptide (TLQP-21) and an immune mediator (C3a) represents a potential broad-spectrum mechanism throughout the CNS for integration of neuroimmune crosstalk at the molecular level.
补体 3a 受体 (C3aR1) 在病理条件下参与小胶质细胞信号转导，最近研究表明其可被神经肽 TLQP-21 激活。我们之前的研究表明，TLQP-21 通过脊髓中未知机制引发痛觉过敏，并导致神经损伤诱导的过敏。在这里，我们确定该机制需要 C3aR1，并且小胶质细胞是 TLQP-21 的细胞靶标。我们提出了一个新的神经免疫信号通路，涉及 TLQP-21 诱导的小胶质细胞 C3aR1 激活，进而有助于脊髓神经可塑性和神经病理性疼痛。这种独特的双重配体激活 C3aR1，由神经肽 (TLQP-21) 和免疫介质 (C3a) 组成，代表了整个中枢神经系统中整合神经免疫串扰的潜在广谱机制，在分子水平上进行。
