Requirement for the basic helix-loop-helix transcription factor Dec2 in initial T(H)2 lineage commitment

How naïve CD4(+) T cells commit to the T helper type 2 (T(H)2) lineage is poorly understood. Here we show that the basic helix-loop-helix transcription factor Dec2 is selectively expressed in T(H)2 cells. CD4(+) T cells from Dec2-deficient mice exhibits defective T(H)2 differentiation in vitro and in vivo in an asthma model and in response to challenge with a parasite antigen. Dec2 promotes interleukin 4 (IL-4), IL-5 and IL-13 expression during early T(H)2 differentiation, and directly binds to and activates transcription of the Junb and Gata3 genes. As GATA3 induces Dec2 expression, these findings also indicate a feed-forward regulatory circuit during T(H)2 differentiation.