Requirement for the basic helix-loop-helix transcription factor Dec2 in initial TH2 lineage commitment.
How naive 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 was selectively expressed in T(H)2 cells. CD4(+) T cells from Dec2-deficient mice showed defective T(H)2 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 T(H)2 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 T(H)2 differentiation.
Yang
Xuexian O
XO
Department of Immunology, MD Anderson Cancer Center, Houston, Texas, USA.
Angkasekwinai
Pornpimon
P
Zhu
Jinfang
J
Peng
Juan
J
Liu
Zhiduo
Z
Nurieva
Roza
R
Liu
Xikui
X
Chung
Yeonseok
Y
Chang
Seon Hee
SH
Sun
Bing
B
Dong
Chen
C
D000818:Animals; D001249:Asthma / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D004195:Disease Models, Animal; D050990:GATA3 Transcription Factor / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency / Q000276:immunology* / Q000378:metabolism
C470968:Bhlhb3 protein, mouse; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors