The Ets-1 transcription factor is required for the development of natural killer cells in mice

Immunity. 1998 Oct;9(4):555-63. doi: 10.1016/s1074-7613(00)80638-x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Differentiation
  • Cytokines / immunology
  • Cytotoxicity, Immunologic
  • Female
  • Hematopoiesis / genetics
  • Hematopoiesis / immunology
  • In Vitro Techniques
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neoplasms, Experimental / etiology
  • Neoplasms, Experimental / immunology
  • Phenotype
  • Proto-Oncogene Protein c-ets-1
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / immunology*
  • Proto-Oncogene Proteins c-ets
  • Receptors, Cytokine / immunology
  • Spleen / cytology
  • Spleen / immunology
  • Transcription Factors / genetics
  • Transcription Factors / immunology*

Substances

  • Cytokines
  • Ets1 protein, mouse
  • Proto-Oncogene Protein c-ets-1
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ets
  • Receptors, Cytokine
  • Transcription Factors