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The role of Notch signaling in Th2 cell differentiation

Terry Fang-2007-01-01-Scholarly Commons (University of Pennsylvania)
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TL;DRAbstract

Notch signaling is an evolutionarily conserved pathway that is involved in diverse cell fate decisions. Notch ligands and receptors have been implicated in helper T cell (Th) differentiation. To determine if Notch signals are involved in differentiation of T helper type 1 (Th1) cells, Th2 cells, or both, mice were generated that conditionally inactivate Notch signaling in mature T cells. Mice that lack Notch signaling in CD4+ T cells fail to develop a protective Th2 response against the gastrointestinal helminth Trichuris muris. In contrast, they exhibit effective Th1 responses and are able to control Leishmania major infection. Notch has a direct role in regulating Gata3 and IL-4 during Th2 differentiation. Notch targets the promoter of an alternative exon of Gata3 to induce Gata3 expression in CD4+ T cells. In addition, GATA-3 acts in parallel with Notch to synergistically activate IL-4 expression. The findings presented here identify a novel role for a highly conserved developmental

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Notch signaling is an evolutionarily conserved pathway that is involved in diverse cell fate decisions. Notch ligands and receptors have been implicated in helper T cell (Th) differentiation. To determine if Notch signals are involved in differentiation of T helper type 1 (Th1) cells, Th2 cells, or both, mice were generated that conditionally inactivate Notch signaling in mature T cells. Mice that lack Notch signaling in CD4+ T cells fail to develop a protective Th2 response against the gastrointestinal helminth Trichuris muris. In contrast, they exhibit effective Th1 responses and are able to control Leishmania major infection. Notch has a direct role in regulating Gata3 and IL-4 during Th2 differentiation. Notch targets the promoter of an alternative exon of Gata3 to induce Gata3 expression in CD4+ T cells. In addition, GATA-3 acts in parallel with Notch to synergistically activate IL-4 expression. The findings presented here identify a novel role for a highly conserved developmental

Keywords

Notch signaling pathwayCell biologyCellular differentiationSignal transductionChemistryBiologyGeneticsGene

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