Requirement for the basic helix-loop-helix transcription factor Dec2 in initial TH2 lineage commitment

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Abstract
The molecular mediators responsible for directing T helper type 2 (TH2) differentiation remain incompletely defined. Dong and co-workers find that the transcription factor Dec2 promotes expression of the transcription factor JunB and is essential for the induction of TH2 responses. How naive CD4+ T cells commit to the T helper type 2 (TH2) lineage is poorly understood. Here we show that the basic helix-loop-helix transcription factor Dec2 was selectively expressed in TH2 cells. CD4+ T cells from Dec2-deficient mice showed defective TH2 differentiation in vitro and in vivo in an asthma model and in response to challenge with a parasite antigen. Dec2 promoted expression of interleukin 4 (IL-4), IL-5 and IL-13 during early TH2 differentiation and directly bound to and activated transcription of genes encoding the transcription factors JunB and GATA-3. As GATA-3 induces Dec2 expression, our findings also indicate a feed-forward regulatory circuit during TH2 differentiation.