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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Basic-Leucine Zipper Transcription Factors / biosynthesis
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Basic-Leucine Zipper Transcription Factors / genetics
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Basic-Leucine Zipper Transcription Factors / immunology*
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Basic-Leucine Zipper Transcription Factors / metabolism
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CD8 Antigens / genetics
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CD8 Antigens / immunology*
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CD8 Antigens / metabolism
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / metabolism
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Cell Differentiation / genetics
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Cell Differentiation / immunology*
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Dendritic Cells / cytology
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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Gene Expression Regulation / genetics
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Gene Expression Regulation / immunology
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Interleukin-12 / genetics
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Interleukin-12 / immunology
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Interleukin-12 / metabolism
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Membrane Proteins / genetics
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Membrane Proteins / immunology
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Membrane Proteins / metabolism
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Mice
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Mice, Knockout
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Plasma Cells / cytology
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Plasma Cells / immunology*
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Plasma Cells / metabolism
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Repressor Proteins / biosynthesis
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Repressor Proteins / genetics
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Repressor Proteins / immunology
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Toll-Like Receptor 3 / genetics
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Toll-Like Receptor 3 / immunology
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Toll-Like Receptor 3 / metabolism
Substances
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Basic-Leucine Zipper Transcription Factors
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CD8 Antigens
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CD8 antigen, alpha chain
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Membrane Proteins
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Nfil3 protein, mouse
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Repressor Proteins
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SNFT protein, mouse
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TLR3 protein, mouse
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Toll-Like Receptor 3
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flt3 ligand protein
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Interleukin-12