Transcriptome-Based Network Analysis Reveals a Spectrum Model of Human Macrophage Activation

被引：1814

作者：

Xue, Jia ^{[1
]}

Schmidt, Susanne V. ^{[1
]}

Sander, Jil ^{[1
]}

Draffehn, Astrid ^{[1
]}

Krebs, Wolfgang ^{[1
]}

Quester, Inga ^{[1
]}

De Nardo, Dominic ^{[2
]}

Gohel, Trupti D. ^{[1
]}

Emde, Martina ^{[1
]}

Schmidleithner, Lisa ^{[1
]}

Ganesan, Hariharasudan ^{[1
]}

Nino-Castro, Andrea ^{[1
]}

Mallmann, Michael R. ^{[1
]}

Labzin, Larisa ^{[2
]}

Theis, Heidi ^{[1
]}

Kraut, Michael ^{[1
]}

Beyer, Marc ^{[1
]}

Latz, Eicke ^{[2
,3
,4
]}

Freeman, Tom C. ^{[5
,6
]}

Ulas, Thomas ^{[1
]}

Schultze, Joachim L. ^{[1
]}

机构：

[1] Univ Bonn, LIMES Inst, D-53115 Bonn, Germany

[2] Univ Bonn, Univ Hosp, Inst Innate Immun, D-53127 Bonn, Germany

[3] UMass Med Sch, Div Infect Dis & Immunol, Worcester, MA 01605 USA

[4] German Ctr Neurodegenerat Dis DZNE, D-53127 Bonn, Germany

[5] Univ Edinburgh, Roslin Inst, Edinburgh EH25 9RG, Midlothian, Scotland

[6] Univ Edinburgh, Royal Dick Sch Vet Studies, Edinburgh EH25 9RG, Midlothian, Scotland

来源：

IMMUNITY | 2014年 / 40卷 / 02期

基金：

英国生物技术与生命科学研究理事会;

关键词：

GENE-EXPRESSION; REGULATORY NETWORK; DENDRITIC CELLS; MOUSE; POLARIZATION; INFECTION; PROGRAMS; DIFFERENTIATION; CONSERVATION; DIVERGENCE;

D O I：

10.1016/j.immuni.2014.01.006

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

Macrophage 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.

引用

页码：274 / 288

页数：15

共 53 条

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