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HMBOX1 negatively regulates NK cell functions by suppressing the NKG2D/DAP10 signaling pathway

Cellular & Molecular Immunology volume 8, pages 433–440 (2011)Cite this article

Abstract

HMBOX1 is a new member of the homeobox family. Homeobox members have been reported to participate in embryonic development and systemic metabolism, but the function of HMBOX1 remains unclear, especially in the hematopoietic system. Here, we show that HMBOX1 is expressed at a high level in primary human NK cells but is expressed at much lower levels in NK cell lines. Overexpression of HMBOX1 significantly inhibited NK cell activities, including natural cytotoxicity against tumor cells, the level of CD107a (a marker protein for degranulation) and the production of cytolytic proteins (perforin and granzymes). More interestingly, HMBOX1 negatively regulated the expression of NKG2D and the activation of the NKG2D/DAP10 signaling pathway in NK cells. This effect was reversed by knocking down HMBOX1. Taken together, these findings demonstrate that HMBOX1 may act as a negative regulator of NK cell functions via suppressing the NKG2D/DAP10 signaling pathway.

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Acknowledgements

This work was supported by the Natural Science Foundation of China (30901307 and 30671901) and the Ministry of Science and Technology of China (2007AA021000, 2007AA021109 and 2006CB504303).

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  1. Dr J Zhang, Institute of Immunopharmacology and Immunotherapy, School of Pharmaceutical Sciences, Shandong University, 44 Wenhua West Road, Jinan 250012, China. E-mail: zhangj65@sdu.edu.cn

Authors and Affiliations

  1. School of Pharmaceutical Sciences, Shandong University, Jinan, China

    Longyan Wu, Cai Zhang & Jian Zhang

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Wu, L., Zhang, C. & Zhang, J. HMBOX1 negatively regulates NK cell functions by suppressing the NKG2D/DAP10 signaling pathway. Cell Mol Immunol 8, 433–440 (2011). https://doi.org/10.1038/cmi.2011.20

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