The alternative macrophage relay: STAT6 passes the baton to EGR2

Alternative polarization of macrophages induced by IL-4 is important for homeostasis and tissue repair. Downstream from IL-4 receptor signaling, STAT6 activation is transient, but induces stable transcriptional changes. These data suggest that STAT6 induces second messengers to carry out the alternative transcriptional program. In this issue of Genes & Development, Daniel and colleagues (pp. 1474–1492) identify EGR2 as a downstream regulator of STAT6 with broad functionality that further induces many transcription factors associated with alternative polarization. Identification of high EGR2 expression in a subset of mouse and human alveolar macrophages further highlights EGR2 as a conserved marker of alternatively activated macrophages.