Spinal macrophages resolve nociceptive hypersensitivity after peripheral injury.
Spinal macrophages resolve nociceptive hypersensitivity after peripheral injury.
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DOI：
10.1016/j.neuron.2021.02.018
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发表时间：
2021-04-21
期刊：
影响因子：
16.2
通讯作者：
Zylka MJ
中科院分区：
文献类型：
--
作者：
Niehaus JK;Taylor-Blake B;Loo L;Simon JM;Zylka MJ
周围神经损伤诱导脊髓神经胶质细胞中促进神经性疼痛的长期促炎反应，但尚未确定解决脊髓炎症的内源性细胞的身份。在单细胞RNA-seq（scRNAseq）的指导下，我们发现MRC 1+脊髓巨噬细胞在浅表损伤（SI，神经完整）后增殖并上调抗炎介质Cd 163，然而这种反应在神经损伤动物中减弱。消耗SI动物的脊髓巨噬细胞促进小胶质细胞增生，并导致机械超敏反应持续存在。相反，在脊髓巨噬细胞中表达Cd 163增加了白细胞介素10的表达，减弱了微小和星形胶质细胞增生，并极大地减轻了神经损伤动物的机械和热超敏反应。我们的数据表明，MRC 1+脊髓巨噬细胞积极抑制神经胶质细胞，以限制神经炎症，并解决浅表损伤后的机械性疼痛。此外，我们发现，神经损伤动物的脊髓巨噬细胞的抗炎反应减弱，但可以治疗性地诱导，以促进神经性疼痛的持久恢复。周围神经损伤引起脊髓炎症和神经性疼痛。在单细胞RNA-seq的指导下，Niehaus等人鉴定了一类脊髓巨噬细胞，可以通过治疗诱导来解决小胶质细胞增生并促进神经性疼痛的持久恢复。
Peripheral nerve injury induces long-term pro-inflammatory responses in spinal cord glial cells that facilitate neuropathic pain, but the identity of endogenous cells that resolve spinal inflammation has not been determined. Guided by single-cell RNA-seq (scRNAseq), we found that MRC1+ spinal cord macrophages proliferated and upregulated the anti-inflammatory mediator Cd163 in mice following superficial injury (SI, nerve intact), however this response was blunted in nerve-injured animals. Depleting spinal macrophages in SI animals promoted microgliosis and caused mechanical hypersensitivity to persist. Conversely, expressing Cd163 in spinal macrophages increased Interleukin 10 expression, attenuated micro- and astrogliosis, and enduringly alleviated mechanical and thermal hypersensitivity in nerve-injured animals. Our data indicate that MRC1+ spinal macrophages actively restrain glia, to limit neuroinflammation, and resolve mechanical pain following a superficial injury. Moreover, we show that spinal macrophages from nerve-injured animals mount a dampened anti-inflammatory response but can be therapeutically coaxed to promote long-lasting recovery of neuropathic pain. Peripheral nerve injury causes inflammation in the spinal cord and neuropathic pain. Guided by single-cell RNA-seq, Niehaus et al. identify a class of spinal macrophages that can be therapeutically coaxed to resolve microgliosis and promote long-lasting recovery of neuropathic pain.
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