Abstract
Type 1 regulatory T cells (Tr1 cells) are induced by interleukin-27 (IL-27) and have critical roles in the control of autoimmunity and resolution of inflammation. We found that the transcription factors IRF1 and BATF were induced early on after treatment with IL-27 and were required for the differentiation and function of Tr1 cells in vitro and in vivo. Epigenetic and transcriptional analyses revealed that both transcription factors influenced chromatin accessibility and expression of the genes required for Tr1 cell function. IRF1 and BATF deficiencies uniquely altered the chromatin landscape, suggesting that these factors serve a pioneering function during Tr1 cell differentiation.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Autoimmune Diseases / genetics
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Autoimmune Diseases / immunology
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Autoimmune Diseases / metabolism
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Autoimmunity
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Basic-Leucine Zipper Transcription Factors / genetics
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Basic-Leucine Zipper Transcription Factors / metabolism*
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Cell Differentiation / genetics
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Cell Differentiation / immunology*
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Chromatin / genetics
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Chromatin / metabolism*
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Cluster Analysis
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Cytokines / metabolism
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Cytokines / pharmacology
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Gene Expression Profiling
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Gene Expression Regulation
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Gene Regulatory Networks
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Interferon Regulatory Factor-1 / genetics
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Interferon Regulatory Factor-1 / metabolism*
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Mice
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Mice, Knockout
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Promoter Regions, Genetic
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T-Lymphocyte Subsets / drug effects
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism
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T-Lymphocytes, Regulatory / cytology
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T-Lymphocytes, Regulatory / drug effects
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T-Lymphocytes, Regulatory / immunology*
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T-Lymphocytes, Regulatory / metabolism*
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Transcription Factors / metabolism
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Transcriptome
Substances
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Basic-Leucine Zipper Transcription Factors
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Batf protein, mouse
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Chromatin
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Cytokines
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Interferon Regulatory Factor-1
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Transcription Factors