Abstract
Antiviral immunity and cross-presentation is mediated constitutively through CD8α+ and CD103+ DCs. Development of these DC subsets is thought to require the transcription factors Irf8, Id2, Nfil3, and Batf3, although how this network is regulated is poorly defined. We addressed the nature of the differentiation blocks observed in the absence of these factors and found that although all 4 factors are required for CD103+ DC development, only Irf8 is essential for CD8α+ DCs. CD8α+ DCs emerged in the absence of Id2, Nfil3 and Batf3 in short-term bone marrow reconstitution. These “induced” CD8α+ DCs exhibit several hallmarks of classic CD8α+ DCs including the expression of CD24, Tlr3, Xcr1, Clec9A, and the capacity to cross-present soluble, cell-associated antigens and viral antigens even in the absence of Batf3. Collectively, these results uncover a previously undescribed pathway by which CD8α+ DCs emerge independent of Id2, Nfil3, and Batf3, but dependent on Irf8.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, Viral / immunology
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Basic-Leucine Zipper Transcription Factors / genetics
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Basic-Leucine Zipper Transcription Factors / metabolism
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Basic-Leucine Zipper Transcription Factors / physiology*
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CD8 Antigens / metabolism*
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Cell Differentiation* / genetics
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Cell Differentiation* / immunology
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Cell Survival / genetics
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Cell Survival / immunology
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Cells, Cultured
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Cross-Priming / genetics
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Cross-Priming / immunology
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Cross-Priming / physiology
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Dendritic Cells / immunology
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Dendritic Cells / metabolism
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Dendritic Cells / physiology*
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Herpesvirus 1, Human / immunology
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Inhibitor of Differentiation Protein 2 / genetics
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Inhibitor of Differentiation Protein 2 / metabolism
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Inhibitor of Differentiation Protein 2 / physiology*
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Interferon Regulatory Factors / genetics
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Interferon Regulatory Factors / metabolism
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Interferon Regulatory Factors / physiology
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Repressor Proteins / genetics
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Repressor Proteins / metabolism
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Repressor Proteins / physiology*
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transcription Factors / physiology
Substances
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Antigens, Viral
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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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Idb2 protein, mouse
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Inhibitor of Differentiation Protein 2
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Interferon Regulatory Factors
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Nfil3 protein, mouse
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Repressor Proteins
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SNFT protein, mouse
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Transcription Factors
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interferon regulatory factor-8