巨噬细胞极化
转录组
巨噬细胞
生物
细胞生物学
肺泡巨噬细胞
重编程
计算生物学
慢性阻塞性肺病
基因
免疫学
细胞
基因表达
遗传学
医学
体外
精神科
作者
Jia Xue,Susanne V. Schmidt,Jil Sander,Astrid M. Draffehn,Wolfgang Krebs,Inga Quester,Dominic De Nardo,Trupti D. Gohel,Martina Emde,Lisa Schmidleithner,Hariharasudan Ganesan,Andrea Niño‐Castro,Michael R. Mallmann,Larisa I. Labzin,Heidi Theis,Michael Kraut,Marc Beyer,Eicke Latz,Tom C. Freeman,Thomas Ulas,Joachim L. Schultze
出处
期刊:Immunity
[Elsevier]
日期:2014-02-01
卷期号:40 (2): 274-288
被引量:1880
标识
DOI:10.1016/j.immuni.2014.01.006
摘要
Highlights•Macrophages react with specific transcriptional programming upon distinct signals•Activation by TNF, PGE2, and P3C activates a STAT4-associated transcriptional program•NFKB1, JUNB, and CREB1 are central transcription factors of macrophage activation•Inflammatory signatures are lost in alveolar macrophages from COPD patientsSummaryMacrophage activation is associated with profound transcriptional reprogramming. Although much progress has been made in the understanding of macrophage activation, polarization, and function, the transcriptional programs regulating these processes remain poorly characterized. We stimulated human macrophages with diverse activation signals, acquiring a data set of 299 macrophage transcriptomes. Analysis of this data set revealed a spectrum of macrophage activation states extending the current M1 versus M2-polarization model. Network analyses identified central transcriptional regulators associated with all macrophage activation complemented by regulators related to stimulus-specific programs. Applying these transcriptional programs to human alveolar macrophages from smokers and patients with chronic obstructive pulmonary disease (COPD) revealed an unexpected loss of inflammatory signatures in COPD patients. Finally, by integrating murine data from the ImmGen project we propose a refined, activation-independent core signature for human and murine macrophages. This resource serves as a framework for future research into regulation of macrophage activation in health and disease.Graphical abstract
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