1. NFIL3/E4BP4 is a key transcription factor for CD8α⁺ dendritic cell development.
- Author
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Kashiwada M, Pham NL, Pewe LL, Harty JT, and Rothman PB
- Subjects
- Animals, Basic-Leucine Zipper Transcription Factors biosynthesis, Basic-Leucine Zipper Transcription Factors genetics, Basic-Leucine Zipper Transcription Factors metabolism, CD8 Antigens genetics, CD8 Antigens metabolism, CD8-Positive T-Lymphocytes cytology, CD8-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes metabolism, Cell Differentiation genetics, Dendritic Cells cytology, Dendritic Cells metabolism, Gene Expression Regulation genetics, Gene Expression Regulation immunology, Interleukin-12 genetics, Interleukin-12 immunology, Interleukin-12 metabolism, Membrane Proteins genetics, Membrane Proteins immunology, Membrane Proteins metabolism, Mice, Mice, Knockout, Plasma Cells cytology, Plasma Cells metabolism, Repressor Proteins biosynthesis, Repressor Proteins genetics, Repressor Proteins immunology, Toll-Like Receptor 3 genetics, Toll-Like Receptor 3 immunology, Toll-Like Receptor 3 metabolism, Basic-Leucine Zipper Transcription Factors immunology, CD8 Antigens immunology, Cell Differentiation immunology, Dendritic Cells immunology, Plasma Cells immunology
- Abstract
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 CD8α(+) conventional DCs (cDCs). 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 through Batf3 expression. Importantly, Nfil3(-/-) mice exhibited impaired cross-priming of CD8(+) T cells against cell-associated antigen, a process normally performed by CD8α(+) cDCs, and failed to produce IL-12 after TLR3 stimulation. Thus, NFIL3 plays an essential role in the development of CD8α(+) cDCs.
- Published
- 2011
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