STAT4 and T-bet are required for the plasticity of IFN-γ expression across Th2 ontogeny and influence changes in Ifng promoter DNA methylation
| Autor: | Christopher L. Williams, Keunwook Lee, Mark Boothby, Marcia M. Schilling, Aditi, Mei Wei, Sung Hoon Cho |
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| Rok vydání: | 2013 |
| Předmět: |
Cellular differentiation
Immunology Population Mice Nude Biology Lymphocyte Activation Article Interferon-gamma Mice Th2 Cells medicine Immunology and Allergy Animals Interferon gamma IL-2 receptor education Promoter Regions Genetic STAT4 Interleukin 4 Cells Cultured Mice Knockout education.field_of_study Mice Inbred BALB C Cell Differentiation Methylation DNA Methylation STAT4 Transcription Factor Th1 Cells Cell biology DNA methylation Cancer research CpG Islands Interleukin-4 T-Box Domain Proteins Immunologic Memory medicine.drug |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 191(2) |
| ISSN: | 1550-6606 |
| Popis: | CD4+ T cells developing toward a Th2 fate express IL-4, IL-5, and IL-13 while inhibiting production of cytokines associated with other Th types, such as the Th1 cytokine IFN- γ. IL-4–producing Th2 effector cells give rise to a long-lived memory population committed to reactivation of the Th2 cytokine gene expression program. However, reactivation of these effector-derived cells under Th1-skewing conditions leads to production of IFN-γ along with IL-4 in the same cell. We now show that this flexibility (“plasticity”) of cytokine expression is preceded by a loss of the repressive DNA methylation of the Ifng promoter acquired during Th2 polarization yet requires STAT4 along with T-box expressed in T cells. Surprisingly, loss of either STAT4 or T-box expressed in T cells increased Ifng promoter CpG methylation in both effector and memory Th2 cells. Taken together, our data suggest a model in which the expression of IFN-γ by Th2-derived memory cells involves attenuation of epigenetic repression in memory Th2 cells, combined with Th1-polarizing signals after their recall activation. |
| Databáze: | OpenAIRE |
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