1. Главная
  2. Ресурсы
  3. Библиотечный поиск
Critical Role for theTranscriptionRegulatorCCCTC-Binding Factorin the Control of Th2Cytokine Expression Claudia Ribeiro de AlmeidaHelen HeathSanja Krpic2009 год

Critical Role for the Transcription Regulator CCCTC-Binding Factor in the Control of Th2 Cytokine Expression
статья из журнала

Страница публикацииПубликация в OpenAlex
Аннотация: Abstract Differentiation of naive CD4+ cells into Th2 cells is accompanied by chromatin remodeling at the Th2 cytokine locus allowing the expression of the IL-4, IL-5, and IL-13 genes. In this report, we investigated the role in Th2 differentiation of the transcription regulator CCCTC-binding factor (CTCF). Chromatin immunoprecipitation analysis revealed multiple CTCF binding sites in the Th2 cytokine locus. Conditional deletion of the Ctcf gene in double-positive thymocytes allowed development of peripheral T cells, but their activation and proliferation upon anti-CD3/anti-CD28 stimulation in vitro was severely impaired. Nevertheless, when TCR signaling was circumvented with phorbol ester and ionomycin, we observed proliferation of CTCF-deficient T cells, enabling the analysis of Th2 differentiation in vitro. We found that in CTCF-deficient Th2 polarization cultures, transcription of IL-4, IL-5, and IL-13 was strongly reduced. By contrast, CTCF deficiency had a moderate effect on IFN-γ production in Th1 cultures and IL-17 production in Th17 cultures was unaffected. Consistent with a Th2 cytokine defect, CTCF-deficient mice had very low levels of IgG1 and IgE in their serum, but IgG2c was close to normal. In CTCF-deficient Th2 cultures, cells were polarized toward the Th2 lineage, as substantiated by induction of the key transcriptional regulators GATA3 and special AT-rich binding protein 1 (SATB1) and down-regulation of T-bet. Also, STAT4 expression was low, indicating that in the absence of CTCF, GATA3 still operated as a negative regulator of STAT4. Taken together, these findings show that CTCF is essential for GATA3- and SATB1-dependent regulation of Th2 cytokine gene expression.
Год издания: 2009
Авторы: Claudia Ribeiro de Almeida, Helen Heath, Sanja Krpic, Gemma M. Dingjan, Jan Piet van Hamburg, Ingrid M. Bergen, Suzanne van de Nobelen, Frank Sleutels, Frank Grosveld, Niels Galjart, Rudi W. Hendriks
Издательство: American Association of Immunologists
Источник: The Journal of Immunology
Ключевые слова: T-cell and B-cell Immunology, Immune Cell Function and Interaction, IL-33, ST2, and ILC Pathways
Другие ссылки: The Journal of Immunology (HTML)
PubMed (HTML)