Human cytomegalovirus drives epigenetic imprinting of the IFNG locus in NKG2Chi natural killer cells.
Human cytomegalovirus drives epigenetic imprinting of the IFNG locus in NKG2Chi natural killer cells.
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人类巨细胞病毒驱动NKG2CHI天然杀伤细胞中IFNG基因座的表观遗传印记。
DOI：
10.1371/journal.ppat.1004441
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发表时间：
2014-10
期刊：
影响因子：
6.7
通讯作者：
Romagnani C
中科院分区：
文献类型：
--
作者：
Luetke-Eversloh M;Hammer Q;Durek P;Nordström K;Gasparoni G;Pink M;Hamann A;Walter J;Chang HD;Dong J;Romagnani C
Memory type 1 T helper (TH1) cells are characterized by the stable expression of interferon (IFN)-γ as well as by the epigenetic imprinting of the IFNG locus. Among innate cells, NK cells play a crucial role in the defense against cytomegalovirus (CMV) and represent the main source of IFN-γ. Recently, it was shown that memory-like features can be observed in NK cell subsets after CMV infection. However, the molecular mechanisms underlying NK cell adaptive properties have not been completely defined. In the present study, we demonstrated that only NKG2Chi NK cells expanded in human CMV (HCMV) seropositive individuals underwent epigenetic remodeling of the IFNG conserved non-coding sequence (CNS) 1, similar to memory CD8+ T cells or TH1 cells. The accessibility of the CNS1 was required to enhance IFN-γ transcriptional activity in response to NKG2C and 2B4 engagement, which led to consistent IFN-γ production in NKG2Chi NK cells. Thus, our data identify epigenetic imprinting of the IFNG locus as selective hallmark and crucial mechanism driving strong and stable IFN-γ expression in HCMV-specific NK cell expansions, providing a molecular basis for the regulation of adaptive features in innate cells. Upon viral infection, the innate interferon (IFN)-γ producing Natural Killer (NK) cells provide fast, but short-term protection, while adaptive T cells confer delayed, but long-lasting immunity. Once acquired, effector properties remain stably imprinted in the T cell memory progeny. Recently, it was shown that human cytomegalovirus (HCMV) infection can shape the human NK cell repertoire and drive the generation and maintenance of NK cell expansions, which express the activating receptor CD94/NKG2C and have been described as memory-like NK cells. However, the molecular mechanisms underlying NK cell adaptive properties driven by HCMV infection have not been completely defined. In this study, we identify epigenetic imprinting of the IFNG locus as selective hallmark and crucial mechanism driving strong and stable IFN-γ expression in HCMV-specific NK cell expansions, thus providing a molecular basis for the regulation of adaptive features in innate cells.
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影响因子：
30.5
作者：
通讯作者：
--
DOI：
10.1084/jem.187.5.813
发表时间：
1998-03-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Borrego F;Ulbrecht M;Weiss EH;Coligan JE;Brooks AG
通讯作者：
Brooks AG
影响因子：
4.8
作者：
Heatley, Susan L.;Pietra, Gabriella;Brooks, Andrew G.
通讯作者：
Brooks, Andrew G.
影响因子：
64.8
作者：
Foster, Simmie L.;Hargreaves, Diana C.;Medzhitov, Ruslan
通讯作者：
Medzhitov, Ruslan
影响因子：
5.4
作者：
Dong, Jun;Chang, Hyun-Dong;Thiel, Andreas
通讯作者：
Thiel, Andreas