SOCS3, a feedback inhibitor of the JAK/STAT signal pathway, negatively regulates axonal regrowth and inflammation in the central nervous system (CNS). Here, we demonstrated a distinct role of SOCS3 in the injured spinal cord of the gecko following tail amputation. Severing the gecko spinal cord did not evoke an inflammatory cascade except for an injury-stimulated elevation of the granulocyte/macrophage colony-stimulating factor (GM-CSF) and interferon gamma (IFN-γ) cytokines. Simultaneously, the expression of SOCS3 was upregulated in microglia, and unexpectedly not in neurons. Enforced expression of SOCS3 was sufficient to suppress the GM-CSF/IFN-γ-driven inflammatory responses through its KIR domain by attenuating the activities of JAK1 and JAK2. SOCS3 was also linked to GM-CSF/IFN-γ-induced cross-tolerance. Transfection of adenovirus overexpressing SOCS3 in the injured cord resulted in a significant decrease of inflammatory cytokines. These results reveal a distinct role of SOCS3 in the regenerating spinal cord, and provide new hints for CNS repair in mammals.

中文翻译：

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SOCS3可减轻脊髓自发再生过程中GM-CSF /IFN-γ介导的炎症。

SOCS3是JAK / STAT信号通路的反馈抑制剂，可负调节中枢神经系统（CNS）的轴突再生和炎症。在这里，我们展示了SOCS3在截肢后壁虎受伤脊髓中的独特作用。切断壁虎脊髓不会引起炎性级联反应，只是损伤刺激的粒细胞/巨噬细胞集落刺激因子（GM-CSF）和干扰素γ（IFN-γ）细胞因子升高。同时，SOCS3的表达在小胶质细胞中上调，而出乎意料的不是在神经元中。SOCS3的增强表达足以通过减弱其JAK1和JAK2的活性，通过其KIR域抑制GM-CSF /IFN-γ驱动的炎症反应。SOCS3也与GM-CSF /IFN-γ诱导的交叉耐受性相关。在受伤的脐带中过度表达SOCS3的腺病毒转染导致炎性细胞因子显着减少。这些结果揭示了SOCS3在再生脊髓中的独特作用，并为哺乳动物中枢神经系统修复提供了新的提示。