The basic leucine zipper transcription factor E4BP4 is essential for natural killer cell development.
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.
Gascoyne
Duncan M
DM
Molecular Haematology and Cancer Biology Unit, University College London Institute of Child Health and Great Ormond Street Hospital for Children, London, UK.
Long
Elaine
E
Veiga-Fernandes
Henrique
H
de Boer
Jasper
J
Williams
Owen
O
Seddon
Benedict
B
Coles
Mark
M
Kioussis
Dimitris
D
Brady
Hugh J M
HJ
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000235:genetics / Q000276:immunology*; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D051797:Inhibitor of Differentiation Protein 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology; D053647:Receptors, Interleukin-15 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology
D050976:Basic-Leucine Zipper Transcription Factors; C497452:Idb2 protein, mouse; D051797:Inhibitor of Differentiation Protein 2; C497441:Nfil3 protein, mouse; D053647:Receptors, Interleukin-15