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An essential role for TAK1 in the contact hypersensitivity response

Cellular & Molecular Immunology volume 8, pages 315–324 (2011)Cite this article

Abstract

Contact hypersensitivity (CHS) is a delayed-type hypersensitivity that can be induced by haptens, such as 2,4-dinitrofluorobenzene (DNFB). Innate and adaptive immunities are both important for the development of CHS. To treat CHS-related diseases, such as allergic contact dermatitis, a disease prevalent in industrialized countries, ways of interfering with improper immune function during CHS responses need to be identified. Transforming growth factor-β-activated kinase-1 (TAK1), a member of mitogen-activated protein kinase kinase kinase family, is important for both innate and adaptive immunities. We thus hypothesized that the CHS response could be inhibited by interfering with TAK1 activity. Using a mouse model in which TAK1 deletion can be locally induced, we observed that TAK deficiency led to an impaired CHS response and was associated with defective T-cell expansion, activation and interferon (IFN)-γ production. In addition, we investigated the effect of deleting TAK1 specifically in dendritic cells (DC) on the CHS response. We found that when TAK1 is deficient in DC, the CHS response was abolished and hapten-elicited T-cell responses were defective. Collectively, this study demonstrates an essential role of TAK1 in the induction of CHS and suggests that targeting TAK1 could be a viable approach to treat CHS.

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Acknowledgements

This work was supported by the National Institutes of Health (R00AI072956 to YYW), the Beijing Natural Science Foundation (7082054), the National Science and Technology Major Specific Project of the People's Republic of China (2009ZX09301-010 to WH) and the China Scholarship Council (YGZ).

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  1. Department of Toxicology, School of Public Health, Peking University, Beijing 100191, China. E-mail: whao@bjmu.edu.cn

Authors and Affiliations

  1. Department of Toxicology, School of Public Health, Peking University, Beijing, China

    Yan G Zhao & Weidong Hao

  2. Department of Microbiology and Immunology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, NC, USA

    Yan G Zhao, Yunqi Wang & Yisong Y Wan

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  1. Yan G Zhao
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  2. Yunqi Wang
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Correspondence to Weidong Hao or Yisong Y Wan.

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Zhao, Y., Wang, Y., Hao, W. et al. An essential role for TAK1 in the contact hypersensitivity response. Cell Mol Immunol 8, 315–324 (2011). https://doi.org/10.1038/cmi.2011.11

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