Opposing macrophage polarization programs show extensive epigenomic and transcriptional cross-talk.
Opposing macrophage polarization programs show extensive epigenomic and transcriptional cross-talk.
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DOI：
10.1038/ni.3710
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发表时间：
2017-05
影响因子：
30.5
通讯作者：
Natoli G
中科院分区：
文献类型：
--
作者：
Piccolo V;Curina A;Genua M;Ghisletti S;Simonatto M;Sabò A;Amati B;Ostuni R;Natoli G
用干扰素-γ（IFN-γ）和白细胞介素4（IL-4）刺激巨噬细胞触发不同且相反的激活程序。在混合感染或癌症期间，巨噬细胞经常暴露于两种细胞因子，但这两种程序如何相互影响仍不清楚。我们发现IFN-γ和IL-4相互抑制由每种细胞因子单独诱导的表观基因组和转录变化。计算和功能分析揭示了基因特异性交叉抑制的基因组基础。例如，虽然STAT 1和IRF 1基序与对IFN-γ的稳健和IL-4抗性应答相关，但它们与辅助转录因子如AP-1的结合位点的共存产生了对IL-4介导的抑制的脆弱性。这些数据提供了一个核心的机制框架的整合信号控制巨噬细胞在复杂的环境条件下激活。
Macrophage stimulation with interferon-γ (IFN-γ) and interleukin 4 (IL-4) triggers distinct and opposing activation programs. During mixed infections or cancer macrophages are often exposed to both cytokines, but how these two programs influence each other remains unclear. We found that IFN-γ and IL-4 mutually inhibited epigenomic and transcriptional changes induced by each cytokine alone. Computational and functional analyses revealed the genomic bases for gene-specific cross-repression. For instance, while STAT1 and IRF1 motifs were associated with robust and IL-4-resistant responses to IFN-γ their coexistence with binding sites for auxiliary transcription factors such as AP-1, generated vulnerability to IL-4-mediated inhibition. These data provide a core mechanistic framework for the integration of signals that control macrophage activation in complex environmental conditions.
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DOI：
10.1038/nri3073
发表时间：
2011-10-14
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
64.5
作者：
Lavin Y;Winter D;Blecher-Gonen R;David E;Keren-Shaul H;Merad M;Jung S;Amit I
通讯作者：
Amit I
影响因子：
16
作者：
Kaikkonen, Minna U.;Spann, Nathanael J.;Heinz, Sven;Romanoski, Casey E.;Allison, Karmel A.;Stender, Joshua D.;Chun, Hyun B.;Tough, David F.;Prinjha, Rab K.;Benner, Christopher;Glass, Christopher K.
通讯作者：
Glass, Christopher K.
影响因子：
30.5
作者：
Monticelli, Silvia;Natoli, Gioacchino
通讯作者：
Natoli, Gioacchino
影响因子：
32.4
作者：
Murray, Peter J.;Allen, Judith E.;Biswas, Subhra K.;Fisher, Edward A.;Gilroy, Derek W.;Goerdt, Sergij;Gordon, Siamon;Hamilton, John A.;Ivashkiv, Lionel B.;Lawrence, Toby;Locati, Massimo;Mantovani, Alberto;Martinez, Fernando O.;Mege, Jean-Louis;Mosser, David M.;Natoli, Gioacchino;Saeij, Jeroen P.;Schultze, Joachim L.;Shirey, Kari Ann;Sica, Antonio;Suttles, Jill;Udalova, Irina;van Ginderachter, Jo A.;Vogel, Stefanie N.;Wynn, Thomas A.
通讯作者：
Wynn, Thomas A.