Abstract
Dendritic cells (DCs) are potent antigen-presenting cells with a pivotal role in antigen-specific immune responses. Here, we found that the helix-loop-helix transcription factor Id2 is up-regulated during DC development in vitro and crucial for the development of distinct DC subsets in vivo. Id2-/- mice lack Langerhans cells (LCs), the cutaneous contingent of DCs, and the splenic CD8alpha+ DC subset is markedly reduced. Mice deficient for transforming growth factor (TGF)-beta also lack LCs, and we demonstrate here that, in DCs, TGF-beta induces Id2 expression. We also show that Id2 represses B cell genes in DCs. These findings reveal a TGF-beta-Id2 signaling pathway in DCs and suggest a mechanism by which Id2 affects the lineage choice of B cell and DC progenitors.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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B-Lymphocytes / metabolism
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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DNA-Binding Proteins / biosynthesis
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / metabolism
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Dendritic Cells / immunology
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Dendritic Cells / metabolism*
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Gene Expression Profiling
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Humans
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Inhibitor of Differentiation Protein 2
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Oligonucleotide Array Sequence Analysis
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Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
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Receptors, Interleukin-4 / metabolism
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Repressor Proteins*
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Transcription Factors / biosynthesis
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Transcription Factors / genetics*
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Transcription Factors / metabolism
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Transforming Growth Factor beta / metabolism
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Up-Regulation
Substances
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DNA-Binding Proteins
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ID2 protein, human
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Inhibitor of Differentiation Protein 2
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Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
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Receptors, Interleukin-4
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Repressor Proteins
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Transcription Factors
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Transforming Growth Factor beta