IκB激酶ε在固有免疫防御及其他方面的作用。
Roles of IκB kinase ε in the innate immune defense and beyond.
作者信息
Zhang Junjie, Tian Mao, Xia Zanxian, Feng Pinghui
机构信息
Department of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, 90033, USA.
State Key Laboratory of Medical Genetics and School of Life Sciences, Central South University, Changsha, 410008, China.
出版信息
Virol Sin. 2016 Dec;31(6):457-465. doi: 10.1007/s12250-016-3898-y. Epub 2016 Dec 28.
Abstract
IκB kinase ε (IKKε) is a non-canonical IκB kinase that is extensively studied in the context of innate immune response. Recently, significant progress has been made in understanding the role of IKKε in interferon (IFN) signaling. In addition to its roles in innate immunity, recent studies also demonstrate that IKKε is a key regulator of the adaptive immune response. Specifically, IKKε functions as a negative feedback kinase to curtail CD8 T cell response, implying that it can be a potential therapeutic target to boost antiviral and antitumor T cell immunity. In this review, we highlight the roles of IKKε in regulating IFN signaling and T cell immunity, and discuss a few imminent questions that remain to be answered.
摘要
IκB激酶ε（IKKε）是一种非经典的IκB激酶，在天然免疫应答的背景下得到了广泛研究。最近，在理解IKKε在干扰素（IFN）信号传导中的作用方面取得了重大进展。除了在天然免疫中的作用外，最近的研究还表明IKKε是适应性免疫应答的关键调节因子。具体而言，IKKε作为负反馈激酶来抑制CD8 T细胞反应，这意味着它可能是增强抗病毒和抗肿瘤T细胞免疫的潜在治疗靶点。在这篇综述中，我们重点介绍了IKKε在调节IFN信号传导和T细胞免疫中的作用，并讨论了一些仍有待解答的紧迫问题。
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PLoS Pathog. 2016 Sep 13;12(9):e1005880. doi: 10.1371/journal.ppat.1005880. eCollection 2016 Sep.
2
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Oncotarget. 2017 Feb 28;8(9):14487-14501. doi: 10.18632/oncotarget.11629.
3
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