Requirement for IRF-1 in the microenvironment supporting development of natural killer cells

Nature. 1998 Feb 12;391(6668):700-3. doi: 10.1038/35636.


Natural killer (NK) cells are critical for both innate and adaptive immunity. The development of NK cells requires interactions between their progenitors and the bone-marrow microenvironment; however, little is known about the molecular nature of such interactions. Mice that do not express the transcription factor interferon-regulatory factor-1 (IRF-1; such mice are IRF-1(-/-) mice) have been shown to exhibit a severe NK-cell deficiency. Here we demonstrate that the lack of IRF-1 affects the radiation-resistant cells that constitute the microenvironment required for NK-cell development, but not the NK-cell progenitors themselves. We also show that IRF-1(-/-) bone-marrow cells can generate functional NK cells when cultured with the cytokine interleukin-15 and that the interleukin-15 gene is transcriptionally regulated by IRF-1. These results reveal, for the first time, a molecular mechanism by which the bone-marrow microenvironment supports NK-cell development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / physiology
  • Bone Marrow Transplantation
  • Cell Differentiation / physiology
  • Cells, Cultured
  • Cloning, Molecular
  • DNA-Binding Proteins / physiology*
  • Gene Expression Regulation / drug effects
  • Interferon Regulatory Factor-1
  • Interferon-gamma / pharmacology
  • Interleukin-15 / genetics
  • Interleukin-15 / physiology
  • Killer Cells, Natural / cytology*
  • Killer Cells, Natural / transplantation
  • Lipopolysaccharides / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Phosphoproteins / physiology*
  • RNA, Messenger / metabolism
  • Recombinant Proteins / pharmacology
  • Regulatory Sequences, Nucleic Acid
  • Transcription Factors / physiology*
  • Transplantation Chimera


  • DNA-Binding Proteins
  • Interferon Regulatory Factor-1
  • Interleukin-15
  • Irf1 protein, mouse
  • Lipopolysaccharides
  • Phosphoproteins
  • RNA, Messenger
  • Recombinant Proteins
  • Transcription Factors
  • Interferon-gamma