Suppressor of cytokine signaling 1 regulates the immune response to infection by a unique inhibition of type I interferon activity
Suppressor of cytokine signaling 1 regulates the immune response to infection by a unique inhibition of type I interferon activity
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DOI：
10.1038/ni1287
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发表时间：
2006-01-01
影响因子：
30.5
通讯作者：
Hertzog, PJ
中科院分区：
文献类型：
--
作者：
Fenner, JE;Starr, R;Hertzog, PJ
细胞因子信号转导抑制因子1(SOCS1)是细胞因子信号转导和免疫反应的重要调节因子。SOCS1基因缺陷的小鼠会患上严重的炎症性疾病，但对病毒感染具有很强的抵抗力。使用I型干扰素中和抗体(干扰素-α和干扰素-β)和缺乏干扰素-γ或I型干扰素受体成分的小鼠(IFNAR1或IFNAR2)，我们在这里证明了SOCS1缺陷增强了I型干扰素的抗病毒和促炎作用，而不依赖于干扰素-伽玛。SOCS1抑制I型干扰素反应的机制与其他细胞因子不同。SOCS1结合并调节IFNAR1-而不是IFNAR2-特异性信号，取消转录因子STAT1的酪氨酸磷酸化，并缩短抗病毒基因表达的持续时间。因此，SOCS1是一种重要的体内I型干扰素信号抑制因子，有助于平衡其在天然免疫中有益的抗病毒作用和有害的促炎作用。
Suppressor of cytokine signaling 1 (SOCS1) is a critical regulator of cytokine signaling and immune responses. SOCS1-deficient mice develop severe inflammatory disease, but are very resistant to viral infections. Using neutralizing antibody to type I interferon (IFN-alpha and IFN-beta) and mice deficient in interferon-gamma or type I interferon receptor components (IFNAR1 or IFNAR2), we demonstrate here that SOCS1 deficiency amplified type I interferon antiviral and proinflammatory actions independently of interferon-gamma. The mechanism of the suppression of type I interferon responses by SOCS1 was distinct from that of other cytokines. SOCS1 associated with and regulated IFNAR1- but not IFNAR2-specific signals, abrogating tyrosine phosphorylation of transcription factor STAT1 and reducing the duration of antiviral gene expression. Thus, SOCS1 is an important in vivo inhibitor of type I interferon signaling and contributes to balancing its beneficial antiviral versus detrimental proinflammatory effects on innate immunity.