Dec2 promotes Th2 cell differentiation by enhancing IL-2R signaling.
Th cell differentiation is precisely regulated by thousands of genes at different stages. In the present study, we demonstrate that Dec2, a transcription factor belonging to the bHLH (basic helix-loop-helix) superfamily, is progressively induced during the course of Th2 differentiation, especially at the late stage. The up-regulated Dec2 can strongly promote Th2 development under Th2-inducing conditions, as evidenced by retrovirus-mediated gene transfer or transgenic manipulation. In addition, an enhancement of Th2 responses is also detectable in Dec2 transgenic mice in vivo. Conversely, RNA interference-mediated suppression of endogenous Dec2 could attenuate Th2 differentiation. Finally, we show that the enhanced Th2 development is at least in part due to substantial up-regulation of CD25 expression elicited by Dec2, thereby resulting in hyperresponsiveness to IL-2 stimulation.
Liu
Zhiduo
Z
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Li
Zhenhu
Z
Mao
Kairui
K
Zou
Jia
J
Wang
Yuan
Y
Tao
Zhiyun
Z
Lin
Guomei
G
Tian
Lin
L
Ji
Yongyong
Y
Wu
Xiaodong
X
Zhu
Xueliang
X
Sun
Shuhui
S
Chen
Weiguang
W
Xiang
Charlie
C
Sun
Bing
B
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005260:Female; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D034741:RNA, Small Interfering / Q000276:immunology / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000276:immunology* / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation / Q000276:immunology
C470968:Bhlhb3 protein, mouse; D016207:Cytokines; D007376:Interleukin-2; D034741:RNA, Small Interfering; D015375:Receptors, Interleukin-2; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D014157:Transcription Factors; D015847:Interleukin-4; D010047:Ovalbumin