SOCS3 Attenuates GM-CSF/IFN-γ-Mediated Inflammation During Spontaneous Spinal Cord Regeneration

• 作者: Bingqiang He Hui Li Nan Du Tiancheng Song Wenjuan Wang Xingxing Gu Xuejie Zhang Yi Luo Yingjie Wang Yongjun Wang Yue Zhou
• 来源期刊: 神经科学通报（英文版）
• 年，卷（期）: 2020,（7）
• 页码范围: 778-792
• 页数: 15页
• 语种: 英文

摘要

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 GMCSF/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.