Department of Anesthesiology, Changhai Hospital, The Second Military Medical University, Shanghai, 200433, China.
Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, 200032, China.
Sci Rep. 2018 Jan 8;8(1):51. doi: 10.1038/s41598-017-18357-z.
Increasing evidence suggests that T cells and glia participate in the process of neuropathic pain. However, little is known about the involvement of T cells or the interaction between glia and T cells at the molecular level. Here we investigated the phenotype of T cell infiltration into the spinal cord in inflammatory pain and explored potential crosstalk between glia and T cells. The establishment of monoarthritis produced T cell infiltration and astrocyte activation, exhibiting similar kinetics in the spinal cord. T-cell-deficient (Rag1) mice significantly attenuated MA-induced mechanical allodynia and GFAP upregulation. Double immunofluorescence staining showed that CD3 mainly colocalized with interferon-gamma (IFN-γ). Western blot and flow cytometry showed that multiple intrathecal administrations of astrocytic inhibitor fluorocitrate decreased IFN-γ-production without decreasing T cell number in the spinal cord. Spinal IFN-γ blockade reduced MA-induced mechanical allodynia and astroglial activation. In contrast, treatment with rIFN-γ directly elicited persistent mechanical allodynia and upregulation of GFAP and pJNK1/2 in naïve rats. Furthermore, rIFN-γ upregulated the phosphorylation of NF-κB p65 in cultured astrocytes vitro and spinal dorsal horn vivo. The results suggest that Th1 cells and astrocytes maintain inflammatory pain and imply that there may be a positive feedback loop between these cells via IFN-γ.
越来越多的证据表明 T 细胞和神经胶质细胞参与了神经病理性疼痛的发生过程。然而，对于 T 细胞的参与或神经胶质细胞与 T 细胞之间在分子水平上的相互作用知之甚少。在这里，我们研究了炎症性疼痛中 T 细胞浸润脊髓的表型，并探讨了神经胶质细胞和 T 细胞之间的潜在相互作用。建立单关节炎可导致 T 细胞浸润和星形胶质细胞活化，在脊髓中表现出相似的动力学。T 细胞缺陷型（Rag1）小鼠显著减轻 MA 诱导的机械性痛觉过敏和 GFAP 的上调。双重免疫荧光染色显示 CD3 主要与干扰素-γ（IFN-γ）共定位。Western blot 和流式细胞术显示，多次鞘内给予星形胶质细胞抑制剂氟柠檬酸可减少 IFN-γ 的产生，而不减少脊髓中的 T 细胞数量。脊髓 IFN-γ 阻断减少 MA 诱导的机械性痛觉过敏和星形胶质细胞活化。相反，在未经处理的大鼠中，rIFN-γ 的直接给药会引起持续的机械性痛觉过敏和 GFAP 和 pJNK1/2 的上调。此外，rIFN-γ 在体外培养的星形胶质细胞中和体内脊髓背角中上调 NF-κB p65 的磷酸化。这些结果表明 Th1 细胞和星形胶质细胞维持炎症性疼痛，并暗示这些细胞之间可能存在通过 IFN-γ 的正反馈回路。
