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GATA3 and STAT5 – Critical Inducers of the Th2 Fate
Retrovirology volume 2, Article number: S16 (2005)
GATA3 has been implicated as a key factor in commitment of CD4 T cells to the Th2 phenotype. Naïve CD4 T cells cultured without exogenous cytokines induce GATA3 and IL-4 transcription only when stimulated with low concentrations of cognate peptide in the presence of IL-2. Naïve CD4 T cells from mice with a conditional deletion of Gata3 fail to induce IL-4 in response to TCR engagement as do cells cultured in the presence of anti-IL-2. High concentration inhibition of GATA3 and IL-4 expression and of Stat5 signaling is rescued by MEK inhibitors implying that inhibition is mediated through erk action. Infection of cells cultured under Thnull conditions with retroviruses containing GATA3 and constitutively active Stat5a induce a Th2 phenotype and result in full accessibility of the Il4 gene. Further, ChIP analyses reveals that in Th2 cells, Stat5a is bound to DNase I hypersensitive sites in the second exon of the Il4 gene. Thus, both GATA3 and STAT5 are key factors in "opening" the Il4 gene and in inducing the Th2 phenotype. Furthermore, GATA3 proved to be important in Th2 growth. In vivo deletion of Gata3 using OX40-Cre eliminated Th2 responses and allowed the development of IFNg-producing cells in mice infected with Nippostrongylus brasiliensis. Thus, GATA3 serves three functions in Th2 biology; it induces the Th2 fate, represses the Th1 fate and it promotes selective outgrowth of Th2 cells.
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Zhu, J., Yamane, H. & Paul, W.E. GATA3 and STAT5 – Critical Inducers of the Th2 Fate. Retrovirology 2 (Suppl 1), S16 (2005). https://doi.org/10.1186/1742-4690-2-S1-S16
- Selective Outgrowth
- ChIP Analysis
- Hypersensitive Site
- Conditional Deletion
- Exogenous Cytokine