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阻断白细胞介素-7 受体可重塑小胶质细胞的替代激活状态,并促进脊髓损伤后的功能恢复。

Blockade of Interleukin-7 Receptor Shapes Macrophage Alternative Activation and Promotes Functional Recovery After Spinal Cord Injury.

机构信息

Department of Neurosurgery, Southwest Medical University Affiliated Hospital, China.

Department of Neurosurgery, Southwest Medical University Affiliated Hospital, China.

出版信息

Neuroscience. 2018 Feb 10;371:518-527. doi: 10.1016/j.neuroscience.2017.10.022. Epub 2017 Oct 22.

DOI:10.1016/j.neuroscience.2017.10.022
PMID:29069618
Abstract

Macrophages are implicated in the pathological processes and functional recovery of spinal cord injury (SCI). Macrophage activation following inflammation depends on networks of interferons and cytokines. Recent evidence indicate that IL-7 signaling can influence the release of proinflammatory factors, however, its roles in modulating macrophage phenotype and function and whether it could affect the functional recovery of SCI are poorly understood. Here, we show that, in a murine SCI model, IL-7 is promptly and vastly induced in injured spinal cord, and that blockade of IL-7 signaling with anti-IL-7Rα mAb (A7R34) favors the generation of M2 phenotype macrophages by affecting the cytokine productions in T helper (Th)1 and Th2 cells. Furthermore, IL-7 displays strong chemotactic property for macrophages and A7R34 treatment inhibits their infiltration into injured sites in vivo. More importantly, the A7R34 treatment promotes functional recovery after SCI, indicating its therapeutic effects on spinal cord repair. Hence, our study proposes a new therapeutic strategy to treat SCI by blocking IL-7 signaling.

摘要

巨噬细胞参与脊髓损伤 (SCI) 的病理过程和功能恢复。炎症后巨噬细胞的激活依赖于干扰素和细胞因子网络。最近的证据表明,IL-7 信号可以影响促炎因子的释放,然而,它在调节巨噬细胞表型和功能中的作用以及它是否能影响 SCI 的功能恢复尚不清楚。在这里,我们发现在小鼠 SCI 模型中,IL-7 在损伤的脊髓中迅速且广泛地被诱导,并且用抗 IL-7Rα mAb(A7R34)阻断 IL-7 信号会通过影响 Th1 和 Th2 细胞中的细胞因子产生而有利于 M2 表型巨噬细胞的产生。此外,IL-7 对巨噬细胞具有很强的趋化性,A7R34 处理抑制它们在体内向损伤部位的浸润。更重要的是,A7R34 处理促进 SCI 后的功能恢复,表明其对脊髓修复的治疗作用。因此,我们的研究提出了一种通过阻断 IL-7 信号来治疗 SCI 的新治疗策略。

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