The microRNA miR-155 controls CD8(+) T cell responses by regulating interferon signaling.

The microRNA miR-155 controls CD8(+) T cell responses by regulating interferon signaling.
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DOI:
10.1038/ni.2576
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发表时间:
2013-06
期刊:
影响因子:
30.5
通讯作者:
Katsikis, Peter D.
Katsikis, Peter D.
中科院分区:
医学1区
文献类型:
--
作者:
Gracias, Donald T.;Stelekati, Erietta;Hope, Jennifer L.;Boesteanu, Alina C.;Doering, Travis A.;Norton, Jillian;Mueller, Yvonne M.;Fraietta, Joseph A.;Wherry, E. John;Turner, Martin;Katsikis, Peter D.

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我们发现microRNA-155(miR-155)在初级效应和效应记忆CD 8 + T细胞中上调,但在幼稚和中央记忆细胞中较低。在miR-155缺陷(miR-155-KO)小鼠中,抗病毒CD 8 + T细胞应答和病毒清除受损,并且这种缺陷是CD 8 + T细胞固有的,因为miR-155-KO CD 8 + T细胞安装大大降低了初级和记忆应答。相反,miR-155过表达增强了体内抗病毒CD 8 + T细胞应答。miR-155-KO CD 8 + T细胞的基因表达谱显示I型干扰素信号传导和敏感性增加。抑制STAT 1或IRF 7增加体内miR-155-KO CD 8 + T细胞应答。我们报道了miR-155在体内调节IFN反应性和CD 8 + T细胞对病原体的反应中的新作用。
We show that microRNA-155 (miR-155) is upregulated in primary effector and effector memory CD8+ T cells but is low in naive and central memory cells. Anti-viral CD8+ T cell responses and viral clearance were impaired in miR-155 deficient (miR-155-KO) mice, and this defect was intrinsic to CD8+ T cells as miR-155-KO CD8+ T cells mounted greatly reduced primary and memory responses. Conversely, miR-155 overexpression augmented anti-viral CD8+ T cell responses in vivo. Gene expression profiling of miR-155-KO CD8+ T cells revealed increased type I interferon signaling and sensitivity. Inhibiting STAT1 or IRF7 increased miR-155-KO CD8+ T cell responses in vivo. We report a novel role for miR-155 in regulating IFN responsiveness and CD8+ T cell responses against pathogens in vivo.
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