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

Nature Immunology volume 10, pages 1260–1266 (2009)Cite this article

An Author Correction to this article was published on 03 September 2020

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Abstract

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.

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Figure 1: Expression and regulation of Dec2.
Figure 2: Dec2 deficiency results in impaired TH2 differentiation in vitro.
Figure 3: Defective TH2 responses in vivo in the absence of Dec2.
Figure 4: Dec2 is required in allergic asthma disease.
Figure 5: Dec2 is required for early TH2 differentiation.
Figure 6: Dec2 activates TH2 gene expression.
Figure 7: Dec2 and regulates Junb and Gata3 transcription.

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  • 03 September 2020

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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Acknowledgements

We thank S. Rivera and J. Parker-Thornburg of the MD Anderson Genetic Engineered Mouse Facility for help in generating knockout and transgenic animals; K. Murphy (Washington University) for the GFP-RV and GFP-RV-GATA-3 vectors; Y. Belkaid (National Institute of Allergy and Infectious Diseases, National Institutes of Health) for S. mansoni eggs and suggestions; and members of the Dong laboratory for help and discussion. Supported by the National Institutes of Health (C.D. and R.N.), the MD Anderson Center for Targeted Therapy (C.D. and R.N.), the American Heart Association (X.O.Y. and R.N.), the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health (J.Z.), the Ministry of Education of China (J.P.) and the Leukemia and Lymphoma Society (C.D.).

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Authors and Affiliations

  1. Department of Immunology, MD Anderson Cancer Center, Houston, Texas, USA

    Xuexian O Yang, Pornpimon Angkasekwinai, Juan Peng, Roza Nurieva, Xikui Liu, Yeonseok Chung, Seon Hee Chang & Chen Dong

  2. Faculty of Allied Health Sciences, Thammasat University, Pathum-than, Thailand

    Pornpimon Angkasekwinai

  3. Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA

    Jinfang Zhu

  4. Department of Respiratory Diseases, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China

    Juan Peng

  5. Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China

    Zhiduo Liu & Bing Sun

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Contributions

C.D., X.O.Y. and B.S. designed the research, analyzed and interpreted the results; X.O.Y., P.A., J.Z., J.P., Z.L., R.N., X.L., Y.C. and S.H.C. did the experiments; and X.O.Y., B.S. and C.D. prepared the manuscript.

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Correspondence to Xuexian O Yang, Bing Sun or Chen Dong.

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Yang, X., Angkasekwinai, P., Zhu, J. et al. Requirement for the basic helix-loop-helix transcription factor Dec2 in initial TH2 lineage commitment. Nat Immunol 10, 1260–1266 (2009). https://doi.org/10.1038/ni.1821

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