Article abstract


Nature Immunology 10, 1118 - 1124 (2009)
Published online: 13 September 2009 | Corrected online: 5 October 2009 | doi:10.1038/ni.1787



There is an Erratum (June 2010) associated with this Article.

The basic leucine zipper transcription factor E4BP4 is essential for natural killer cell development

Duncan M Gascoyne1,7, Elaine Long1,7, Henrique Veiga-Fernandes2,6, Jasper de Boer1, Owen Williams1, Benedict Seddon3, Mark Coles4, Dimitris Kioussis2 & Hugh J M Brady1,5


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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  1. Molecular Haematology and Cancer Biology Unit, University College London Institute of Child Health and Great Ormond Street Hospital for Children, London, UK.
  2. Division of Molecular Immunology and Cancer Biology Unit, University College London Institute of Child Health and Great Ormond Street Hospital for Children, London, UK
  3. Division of Immune Cell Biology, Medical Research Council National Institute for Medical Research, Mill Hill, London, UK.
  4. Centre for Immunology and Infection, Department of Biology and Hull York Medical School, University of York, UK.
  5. Immunology and Infection Section, Division of Cell and Molecular Biology, Sir Alexander Fleming Building, Imperial College, London, UK.
  6. Present address: Immunobiology Unit, Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Lisboa, Portugal.
  7. These authors contributed equally to this work.

Correspondence to: Hugh J M Brady1,5 e-mail: h.brady@imperial.ac.uk.

* 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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