Abstract
Abstract Antigen presentation by mature dendritic cells (DCs) is the first step for initiating adaptive immune responses. DCs are comprised of heterogeneous functional subsets. However, the molecular mechanisms regulating 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 CD8α+ conventional DC (cDC). Nfil3-/- mice specifically lack CD8α+ cDCs but not CD8α- cDCs or plasmacytoid DCs in lymphoid tissues. Flt3 ligand-dependent generation of CD8α+ cDCs in lymphoid tissues and CD8α+-equivalent cDCs from Nfil3-/- bone marrow cells was also impaired. NFIL3 regulates CD8α+ cDC development in part throuth Batf3 expression. Importantly, Nfil3-/- mice exhibit impaired cross-priming of CD8+ T cells against cell-associated antigen, a process normally carried out by CD8α+ cDCs, and failed to produce IL-12 after TLR3 stimulation. Thus, NFIL3 plays an essential role in the development of CD8α+ cDCs.
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