[HTML][HTML] Notch directly regulates Gata3 expression during T helper 2 cell differentiation

TC Fang, Y Yashiro-Ohtani, C Del Bianco… - Immunity, 2007 - cell.com
TC Fang, Y Yashiro-Ohtani, C Del Bianco, DM Knoblock, SC Blacklow, WS Pear
Immunity, 2007cell.com
Notch signaling plays multiple roles to direct diverse decisions regarding cell fate during T
cell development. During helper T (Th) cell differentiation, Notch is involved in generating
optimal Th2 cell responses. Here, we present data investigating how Notch mediates Th2
cell differentiation. Notch showed a CD4+ T cell intrinsic role in promoting IL-4 expression
that required GATA-3. In the absence of Notch signals, Gata3 expression was markedly
diminished. Introduction of an activated allele of Notch1 into CD4+ T cells led to the specific …
Summary
Notch signaling plays multiple roles to direct diverse decisions regarding cell fate during T cell development. During helper T (Th) cell differentiation, Notch is involved in generating optimal Th2 cell responses. Here, we present data investigating how Notch mediates Th2 cell differentiation. Notch showed a CD4+ T cell intrinsic role in promoting IL-4 expression that required GATA-3. In the absence of Notch signals, Gata3 expression was markedly diminished. Introduction of an activated allele of Notch1 into CD4+ T cells led to the specific and direct upregulation of a developmentally regulated Gata3 transcript that included the exon 1a sequences. Furthermore, Notch acted in parallel with GATA-3 to synergistically activate IL-4 expression. Together, these data implicate Gata3 as a direct transcriptional Notch target that acts in concert with Notch signaling to generate optimal Th2 cell responses.
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