T-bet regulates Th1 responses through essential effects on GATA-3 function rather than on IFNG gene acetylation and transcription
| العنوان: | T-bet regulates Th1 responses through essential effects on GATA-3 function rather than on IFNG gene acetylation and transcription |
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| المؤلفون: | Warren Strober, Yuka Kanno, John J. O'Shea, Jay H. Bream, Takashi Usui, Zheng Ju Yao, J. C. Preiss |
| المصدر: | The Journal of Experimental Medicine |
| بيانات النشر: | The Rockefeller University Press, 2006. |
| سنة النشر: | 2006 |
| مصطلحات موضوعية: | Transcription, Genetic, Cellular differentiation, Immunology, Down-Regulation, GATA3 Transcription Factor, Biology, Article, Histones, Interferon-gamma, Mice, Th2 Cells, Transduction, Genetic, Immunology and Allergy, Animals, Humans, STAT4, Transcription factor, Interleukin 4, Cells, Cultured, Mice, Knockout, Receptors, Interleukin-12, hemic and immune systems, Acetylation, Cell Differentiation, Articles, Receptors, Interleukin, Th1 Cells, Molecular biology, GATA4 Transcription Factor, Retroviridae, T cell differentiation, Interleukin 12, STAT protein, Signal transduction, T-Box Domain Proteins, Protein Processing, Post-Translational, Signal Transduction, Transcription Factors |
| الوصف: | T helper type 1 (Th1) development is facilitated by interrelated changes in key intracellular factors, particularly signal transducer and activator of transcription (STAT)4, T-bet, and GATA-3. Here we show that CD4+ cells from T-bet−/− mice are skewed toward Th2 differentiation by high endogenous GATA-3 levels but exhibit virtually normal Th1 differentiation provided that GATA-3 levels are regulated at an early stage by anti–interleukin (IL)-4 blockade of IL-4 receptor (R) signaling. In addition, under these conditions, Th1 cells from T-bet−/− mice manifest IFNG promotor accessibility as detected by histone acetylation and deoxyribonuclease I hypersensitivity. In related studies, we show that the negative effect of GATA-3 on Th1 differentiation in T-bet−/− cells arises from its ability to suppress STAT4 levels, because if this is prevented by a STAT4-expressing retrovirus, normal Th1 differentiation is observed. Finally, we show that retroviral T-bet expression in developing and established Th2 cells leads to down-regulation of GATA-3 levels. These findings lead to a model of T cell differentiation that holds that naive T cells tend toward Th2 differentiation through induction of GATA-3 and subsequent down-regulation of STAT4/IL-12Rβ2 chain unless GATA-3 levels or function is regulated by T-bet. Thus, the principal function of T-bet in developing Th1 cells is to negatively regulate GATA-3 rather than to positively regulate the IFNG gene. |
| اللغة: | English |
| تدمد: | 1540-9538 0022-1007 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d15874781ae2be4f969cc6debd78710a http://europepmc.org/articles/PMC2118252 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d15874781ae2be4f969cc6debd78710a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15409538 00221007 |
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