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Immunity. 2014 Feb 20;40(2):274-88. doi: 10.1016/j.immuni.2014.01.006. Epub 2014 Feb 13.

Transcriptome-based network analysis reveals a spectrum model of human macrophage activation.

Author information

1
Genomics and Immunoregulation, LIMES-Institute, University of Bonn, 53115 Bonn, Germany.
2
Institute of Innate Immunity, University Hospitals, University of Bonn, 53127 Bonn, Germany.
3
Institute of Innate Immunity, University Hospitals, University of Bonn, 53127 Bonn, Germany; Division of Infectious Diseases and Immunology, UMass Medical School, Worcester, MA 01605, USA; German Center of Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany.
4
The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Edinburgh, Midlothian EH25 9RG, Scotland, UK.
5
Genomics and Immunoregulation, LIMES-Institute, University of Bonn, 53115 Bonn, Germany. Electronic address: j.schultze@uni-bonn.de.

Abstract

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.

PMID:
24530056
PMCID:
PMC3991396
DOI:
10.1016/j.immuni.2014.01.006
[Indexed for MEDLINE]
Free PMC Article

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