First Author | Kashiwada M | Year | 2011 |
Journal | Blood | Volume | 117 |
Issue | 23 | Pages | 6193-7 |
PubMed ID | 21474667 | Mgi Jnum | J:174717 |
Mgi Id | MGI:5140660 | Doi | 10.1182/blood-2010-07-295873 |
Citation | Kashiwada M, et al. (2011) NFIL3/E4BP4 is a key transcription factor for CD8alpha dendritic cell development. Blood 117(23):6193-7 |
abstractText | 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 CD8alpha(+) conventional DCs (cDCs). Nfil3(-/-) mice specifically lack CD8alpha(+) cDCs but not CD8alpha(-) cDCs or plasmacytoid DCs in lymphoid tissues. Flt3 ligand-dependent generation of CD8alpha(+) cDCs in lymphoid tissues and CD8alpha(+)-equivalent cDCs from Nfil3(-/-) bone marrow cells was also impaired. NFIL3 regulates CD8alpha(+) 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 CD8alpha(+) cDCs, and failed to produce IL-12 after TLR3 stimulation. Thus, NFIL3 plays an essential role in the development of CD8alpha(+) cDCs. |