Cytokines and transcription factors play key roles in dendritic cell (DC) development, yet information about regulatory interactions between these signals remains limited. Here we show that the cytokines GM-CSF and Flt3L induce the transcriptional mediators Id2 and E2-2 and control DC lineage diversification by STAT–dependent pathways. We found that STAT5 is required for tissue CD103+ DC generation and plasmacytoid DC (pDC) suppression in steady state or response to GM-CSF. STAT5 stimulates GM-CSF–dependent expression of Id2, which controls CD103+ DC production and pDC inhibition. By contrast, pDCs, but not CD103+ DCs, are dependent on STAT3. Consistently, STAT3 stimulates Flt3L-responsive expression of the pDC regulator Tcf4 (E2-2). These data suggest that STATs contribute to DC development by controlling transcription factors involved in lineage differentiation.
