Abstract
Mouse CD4+CD8+ double-positive (DP) thymocytes differentiate into CD4+ helper-lineage cells upon expression of the transcription factor Th-POK but commit to the CD8+ cytotoxic lineage in its absence. We report the redirected differentiation of class I-restricted thymocytes into CD4+CD8- helper-like T cells upon loss of Runx transcription factor complexes. A Runx-binding sequence within the Th-POK locus acts as a transcriptional silencer that is essential for Th-POK repression and for development of CD8+ T cells. Thus, Th-POK expression and genetic programming for T helper cell development are actively inhibited by Runx-dependent silencer activity, allowing for cytotoxic T cell differentiation. Identification of the transcription factors network in CD4 and CD8 lineage choice provides insight into how distinct T cell subsets are developed for regulating the adaptive immune system.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Differentiation
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Cell Lineage
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Chromatin Immunoprecipitation
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Core Binding Factor Alpha 2 Subunit / genetics
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Core Binding Factor Alpha 2 Subunit / physiology*
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Core Binding Factor Alpha 3 Subunit / genetics
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Core Binding Factor Alpha 3 Subunit / physiology*
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Core Binding Factor beta Subunit / metabolism
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Histocompatibility Antigens Class I / immunology
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Histocompatibility Antigens Class II / immunology
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Mice
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Mice, Transgenic
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Molecular Sequence Data
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Silencer Elements, Transcriptional
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T-Lymphocyte Subsets / cytology
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism
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T-Lymphocytes, Cytotoxic / cytology
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T-Lymphocytes, Cytotoxic / immunology*
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T-Lymphocytes, Cytotoxic / metabolism
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T-Lymphocytes, Helper-Inducer / cytology
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T-Lymphocytes, Helper-Inducer / immunology
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T-Lymphocytes, Helper-Inducer / metabolism
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Transcription Factors / genetics
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Transcription Factors / physiology*
Substances
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Cbfb protein, mouse
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Core Binding Factor Alpha 2 Subunit
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Core Binding Factor Alpha 3 Subunit
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Core Binding Factor beta Subunit
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Histocompatibility Antigens Class I
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Histocompatibility Antigens Class II
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Runx1 protein, mouse
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Runx3 protein, mouse
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Th-POK protein, mouse
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Transcription Factors