Transcriptome-Based Network Analysis Reveals a Spectrum Model of
Human Macrophage Activation.
Immunity, (February 2014)DOI: 10.1016/j.immuni.2014.01.006
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.