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Dec2 Promotes Th2 Cell Differentiation by Enhancing IL-2R Signaling¹

Zhiduo Liu,^2* Zhenhu Li,^2* Kairui Mao,^* Jia Zou,^* Yuan Wang,^* Zhiyun Tao,^* Guomei Lin,^* Lin Tian,^* Yongyong Ji,^* Xiaodong Wu,^* Xueliang Zhu,^* Shuhui Sun, Weiguang Chen, Charlie Xiang,³ and Bing Sun^3*

*Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, China; Institute Pasteur of Shanghai, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, China; Fudan University School of Medicine, Shanghai, China; and State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China

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.

³ Address correspondence and reprint requests to Dr. Bing Sun, Laboratory of Molecular Immunology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai, China or Dr. Charlie Xiang, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. E-mail addresses: bsun{at}sibs.ac.cn or cxiang{at}zju.edu.cn

¹ This work was supported by Grants from the National Natural Science Foundation of China (30530700, 30623003, 30600568, 30721065, 90713044, 30600308, 30801011, 30870126) and the CAS project (KSCX1-YW-R-43), a grant from the SIBS project (2007KIP301), grants from the Ministry of Science and Technology (2006CB504300, 2007CB512404, 2006AA02A247, 20072714), grants from the Technology Commission of Shanghai Municipality (88014199, 07DZ22916, 07XD14033, 064319034, 08431903004, 2008ZX10206, 08DZ2291703), the EU project (FP6-2005-SSP-5-B, SP5B-CT-2006-044161), the National Basic Research Program of China (973 Program, No. 2007CB513001) and a grant from the E-institutes of Shanghai Universities Immunology Division.

² Z. Liu and Z. Li contributed equally to this study.