Critical roles of interferon regulatory factor 4 in CD11bhighCD8α– dendritic cell development

IFN regulatory factors (IRFs) are a family of transcription factors that play an essential role in the homeostasis and function of immune systems. Recent studies indicated that IRF-8 is critical for the development of CD11b low CD8α + conventional dendritic cells (DCs) and plasmacytoid DCs. Here we show that IRF-4 is important for CD11b high CD8α – conventional DCs. The development of CD11b high DCs from bone marrow of IRF-4 –/– mice was severely impaired in two culture systems supplemented with either GM-CSF or Flt3-ligand. In the IRF-4 –/– spleen, the number of CD4 + CD8α – DCs, a major subset of CD11b high DCs, was severely reduced. IRF-4 and IRF-8 were expressed in the majority of CD11b high CD4 + CD8α – DCs and CD11b low CD8α + DCs, respectively, in a mutually exclusive manner. These results imply that IRF-4 and IRF-8 selectively play critical roles in the development of the DC subsets that express them.