Abstract
Natural killer (NK) cells are a subset of lymphocytes crucial for innate immunity and modification of adaptive immune responses. In contrast to commitment to the T cell or B cell lineage, little is known about NK cell lineage commitment. Here we show that the basic leucine zipper (bZIP) transcription factor E4BP4 (also called NFIL3) is essential for generation of the NK cell lineage. E4BP4-deficient mice (Nfil3−/–; called 'E4bp4−/–' here) had B cells, T cells and NKT cells but specifically lack NK cells and showed severely impaired NK cell–mediated cytotoxicity. Overexpression of E4bp4 was sufficient to increase NK cell production from hematopoietic progenitor cells. E4BP4 acted in a cell-intrinsic manner 'downstream' of the interleukin 15 receptor (IL-15R) and through the transcription factor Id2. E4bp4−/− mice may provide a model for definitive analysis of the contribution of NK cells to immune responses and pathologies.
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Change history
05 October 2009
NOTE: In the version of this article initially published, the equal contribution of Duncan M. Gascoyne and Elaine Long is not noted. The error has been corrected in the HTML and PDF versions of the article.
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Acknowledgements
We thank J. Zhuang (University of Liverpool) for pMSCV-Mcl-1; M. Woodward (King's College London) for pMSCV-E4bp4; A. O'Garra (Medical Research Council, National Institute for Medical Research) and A. Potocnik (Medical Research Council, National Institute for Medical Research) for additional reagents; and A. Eddaoudi for help with cell sorting. Supported by Children with Leukaemia (H.J.M.B.) and the Leukaemia Research Fund.
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D.M.G., E.L., H.V.-F., J.d.B., O.W. and B.S. did experiments; D.M.G., O.W., M.C., D.K. and H.J.M.B. designed experiments; D.M.G. and H.J.M.B. wrote the manuscript; and H.J.M.B. directed the research.
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Gascoyne, D., Long, E., Veiga-Fernandes, H. et al. The basic leucine zipper transcription factor E4BP4 is essential for natural killer cell development. Nat Immunol 10, 1118–1124 (2009). https://doi.org/10.1038/ni.1787
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DOI: https://doi.org/10.1038/ni.1787
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