The Ets-1 transcription factor is required for the development of natural killer cells in mice.
In this report we have investigated the role of the Ets-1 transcription factor in the differentiation of the NK cell lineage in mice. Splenic NK cells express high levels of Ets-1. Ets-1-deficient mice produced by gene targeting developed mature erythrocytes, monocytes, neutrophils, and T and B lymphocytes. However, spleens from the Ets-1-deficient mice contained significantly reduced numbers of natural killer (NK) cells, and splenocytes from these mice lacked detectable cytolytic activity against NK cell targets in vitro. Moreover, unlike wild-type animals, Ets-1-deficient mice developed tumors following subcutaneous injection of NK-susceptible RMA-S cells. These NK cell defects could not be correlated with defects in the expression of IL-12, IL-15, and IL-18 or the IL-2 or IL-15 receptors. Thus, Ets-1 defines a novel transcriptional pathway that is required for the development of the NK cell lineage in mice.
Barton
K
K
Department of Medicine, The University of Chicago, Illinois 60637, USA.
Muthusamy
N
N
Fischer
C
C
Ting
C N
CN
Walunas
T L
TL
Lanier
L L
LL
Leiden
J M
JM
D000818:Animals; D002454:Cell Differentiation; D016207:Cytokines / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005260:Female; D006410:Hematopoiesis / Q000235:genetics / Q000276:immunology; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009374:Neoplasms, Experimental / Q000209:etiology / Q000276:immunology; D010641:Phenotype; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology*; D050783:Proto-Oncogene Proteins c-ets; D018121:Receptors, Cytokine / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology*
D016207:Cytokines; C494042:Ets1 protein, mouse; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D018121:Receptors, Cytokine; D014157:Transcription Factors