Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
Cell Death Dis. 2013 Jul 4;4(7):e710. doi: 10.1038/cddis.2013.234.
Transfer of type-1 helper T-conditioned (Th1-conditioned) cells promotes functional recovery with enhanced axonal remodeling after spinal cord injury (SCI). This study explored the molecular mechanisms underlying the beneficial effects of pro-inflammatory Th1-conditioned cells after SCI. The effect of Th1-conditioned cells from interferon-γ (ifn-γ) knockout mice (ifn-γ(-/-) Th1 cells) on the recovery after SCI was reduced. Transfer of Th1-conditioned cells led to the activation of microglia (MG) and macrophages (MΦs), with interleukin 10 (IL-10) upregulation. This upregulation of IL-10 was reduced when ifn-γ(-/-) Th1 cells were transferred. Intrathecal neutralization of IL-10 in the spinal cord attenuated the effects of Th1-conditioned cells. Further, IL-10 is robustly secreted from Th1-conditioned cells in an ifn-γ-dependent manner. Th1-conditioned cells from interleukin 10 knockout (il-10(-/-)) mice had no effects on recovery from SCI. These findings demonstrate that ifn-γ-dependent secretion of IL-10 from Th1 cells, as well as native MG/MΦs, is required for the promotion of motor recovery after SCI.
1 型辅助性 T 细胞（Th1 细胞）的转移促进了脊髓损伤（SCI）后的功能恢复和增强的轴突重塑。本研究探讨了 SCI 后促炎 Th1 细胞的有益作用的潜在分子机制。干扰素-γ（IFN-γ）基因敲除小鼠（IFN-γ（-/-）Th1 细胞）的 Th1 细胞对 SCI 后恢复的影响降低。Th1 细胞的转移导致小胶质细胞（MG）和巨噬细胞（MΦ）的激活，白细胞介素 10（IL-10）上调。当转移 IFN-γ（-/-）Th1 细胞时，IL-10 的上调减少。鞘内中和脊髓中的 IL-10 减弱了 Th1 细胞条件的作用。此外，IL-10 以 IFN-γ依赖性方式从 Th1 细胞条件中强烈分泌。来自白细胞介素 10 敲除（IL-10（-/-））小鼠的 Th1 细胞对 SCI 后的恢复没有影响。这些发现表明，IFN-γ依赖性 Th1 细胞分泌的 IL-10 以及天然的 MG/MΦ 是促进 SCI 后运动功能恢复所必需的。
