Abstract
Helper T (Th) cell differentiation is accompanied by complex transcriptional changes. Although costimulatory receptors are important in Th differentiation, the underlying mechanisms are poorly understood. Here we examine the transcriptional mechanisms by which ICOS regulates Th2 differentiation and selective IL-4 expression by effector T cells. We found impaired expression of c-Maf transcription factor functionally associated with the IL-4 defect in ICOS(-/-) cells. c-Maf expression in effector cells was regulated by IL-4 levels during Th differentiation. ICOS costimulation potentiated the T cell receptor (TcR)-mediated initial IL-4 production, possibly through the enhancement of NFATc1 expression. These data indicate that ICOS, by enhancing TcR signals at an early stage of T cell activation, regulates IL-4 transcription and T cell function in effector cells.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigens, Differentiation, T-Lymphocyte / physiology*
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Cell Differentiation / physiology*
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DNA-Binding Proteins / biosynthesis
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DNA-Binding Proteins / genetics
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Gene Expression Regulation / physiology*
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Inducible T-Cell Co-Stimulator Protein
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Interleukin-4 / genetics
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Interleukin-4 / metabolism
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Mice
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Mice, Knockout
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NFATC Transcription Factors
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Nuclear Proteins*
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Proto-Oncogene Proteins / biosynthesis
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins c-maf
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Th2 Cells / physiology*
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Transcription Factors / biosynthesis
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Transcription Factors / genetics
Substances
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Antigens, Differentiation, T-Lymphocyte
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DNA-Binding Proteins
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Icos protein, mouse
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Inducible T-Cell Co-Stimulator Protein
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Maf protein, mouse
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NFATC Transcription Factors
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Nfatc1 protein, mouse
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Nuclear Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-maf
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Transcription Factors
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Interleukin-4