Interferon α/β-mediated inhibition and promotion of interferon γ:: STATI resolves a paradox
Interferon α/β-mediated inhibition and promotion of interferon γ:: STATI resolves a paradox
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DOI：
10.1038/76940
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发表时间：
2000-07-01
影响因子：
30.5
通讯作者：
Biron, CA
中科院分区：
文献类型：
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作者：
Nguyen, KB;Cousens, LP;Biron, CA
诱导高系统水平的I型干扰素（IFN）IFN-α和IFN-β是许多病毒感染的标志。除了其有效的抗病毒作用外，这些细胞因子还介导许多免疫调节功能，并可促进T细胞中IFN-γ的表达。然而，在小鼠病毒感染期间，IFN-γ产生并不总是与全身性IFN-α/β产生同时观察到，并且当在这些时间引起时，是IFN-α β非依赖性的。我们证明，I型干扰素不仅不能诱导，但也起作用，抑制，IFN-γ表达的NK细胞和T细胞，抑制的机制是依赖于IFN-α/β受体和信号转导和转录激活因子I（STATI）。在没有STATI的情况下，不仅IFN-α/β介导的抑制作用完全消除，而且细胞因子本身可以诱导IFN-γ表达。这些结果表明，在对病毒感染的先天性应答时，内源性生化途径能够负调节由IFN-α/β或其他刺激物引起的NK和T细胞IFN-γ表达。他们还表明，I型干扰素信号可以通过STATI依赖性和独立性机制发生，并表明IFN-α/β有效诱导IFN-γ表达需要STATI调节。这种免疫调节途径对于形成针对病毒感染的内源性先天性和病毒特异性适应性免疫应答可能是至关重要的。
Induction of high systemic levels of type I interferons (IFNs) IFN-alpha and IFN-beta is a hallmark of many viral infections. In addition to their potent antiviral effects, these cytokines mediate a number of immunoregulatory functions and can promote IFN-gamma expression in T cells. However, during viral infections of mice IFN-gamma production is not always observed at the same time as systemic IFN-alpha/beta production and when, elicited at these times, is IFN-alp-independent. We demonstrate that type I interferons not only fail to induce, but also act to inhibit, IFN-gamma expression by both NK and T cells,The mechanism of inhibition is dependent upon the IFN-alpha/beta receptor and the signal transducer and activator of transcription I (STATI). In the absence of STATI, not only are the IFN-alpha/beta-mediated inhibitory effects completely abrogated, but the cytokines themselves can induce IFN-gamma expression. These results indicate that endogenous biochemical pathways are in place to negatively regulate NK and T cell IFN-gamma expression elicited by IFN-alpha/beta or other stimuli, at times of innate responses to viral infections. They also show that type I interferon signaling can occur through STATI-dependent and independent mechanisms and suggest that efficient induction of IFN-gamma expression by IFN-alpha/beta requires STATI regulation. Such immunoregulatory pathways may be critical for shaping the endogenous innate and virus-specific adaptive immune responses to viral infections.