NFIL3/E4BP4 is a key transcription factor for CD8α+ dendritic cell development

Antigen presentation by mature dendritic cells (DCs) is the first step for initiating adaptive immune responses. DCs are composed of heterogeneous functional subsets; however, the molecular mechanisms that regulate differentiation of specific DC subsets are not understood. Here, we report that the basic leucine zipper transcription factor NFIL3/E4BP4 is essential for the development of CD8 alpha(+) conventional DCs (cDCs). Nfil3(-/-) mice specifically lack CD8 alpha(+) cDCs but not CD8 alpha(+) cDCs or plasmacytoid DCs in lymphoid tissues. Flt3 ligand-dependent generation of CD8 alpha(+) cDCs in lymphoid tissues and CD8 alpha(+)-equivalent cDCs from Nfil3(-/-) bone marrow cells was also impaired. NFIL3 regulates CD8 alpha(+) cDC development in part through Batf3 expression. Importantly, Nfil3(-/-) mice exhibited impaired cross-priming of CD8(+)T cells against cell-associated antigen, a process normally performed by CD8 alpha(+) cDCs, and failed to produce IL-12 after TLR3 stimulation. Thus, NFIL3 plays an essential role in the development of CD8 alpha(+) cDCs. (Blood. 2011;117(23):6193-6197)