SOCS3 Attenuates GM-CSF/IFN-γ-Mediated Inflammation During Spontaneous Spinal Cord Regeneration
SOCS3 Attenuates GM-CSF/IFN-γ-Mediated Inflammation During Spontaneous Spinal Cord Regeneration
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SOCS3 减轻脊髓自发再生过程中 GM-CSF/IFN-γ 介导的炎症
DOI：
10.1007/s12264-020-00493-8
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发表时间：
2020-04
影响因子：
5.6
通讯作者：
Wang Yongjun
中科院分区：
文献类型：
--
作者：
Zhang Xuejie;He Bingqiang;Li Hui;Wang Yingjie;Zhou Yue;Wang Wenjuan;Song Tiancheng;Du Nan;Gu Xingxing;Luo Yi;Wang Yongjun
SOCS 3是JAK/STAT信号通路的反馈抑制剂，负调节中枢神经系统（CNS）中的轴突再生和炎症。在这里，我们证明了SOCS 3在壁虎断尾后脊髓损伤中的独特作用。切断壁虎脊髓并没有引起炎症级联反应，除了损伤刺激的粒细胞/巨噬细胞集落刺激因子（GM-CSF）和干扰素γ（IFN-γ）细胞因子的升高。同时，SOCS 3的表达在小胶质细胞中上调，而出乎意料地在神经元中未上调。SOCS 3的增强表达足以通过其KIR结构域通过减弱JAK 1和JAK 2的活性来抑制GM-CSF/IFN-γ驱动的炎症反应。SOCS 3还与GM-CSF/IFN-γ诱导的交叉耐受性有关。在损伤的脊髓中转染过表达SOCS 3的腺病毒导致炎性细胞因子的显著减少。这些结果揭示了SOCS 3在脊髓再生中的独特作用，并为哺乳动物的CNS修复提供了新的线索。
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 crosstolerance. 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.