Shared Dependence on the DNA-binding Factor TOX for the Development of Lymphoid Tissue-Inducer Cell and NK Cell Lineages

Nat Immunol. 2010 Oct;11(10):945-52. doi: 10.1038/ni.1930. Epub 2010 Sep 5.


TOX is a DNA-binding factor required for development of CD4(+) T cells, natural killer T cells and regulatory T cells. Here we document that both natural killer (NK) cell development and lymphoid tissue organogenesis were also inhibited in the absence of TOX. We found that the development of lymphoid tissue-inducer cells, a rare subset of specialized cells that has an integral role in lymphoid tissue organogenesis, required TOX. Tox was upregulated considerably in immature NK cells in the bone marrow, consistent with the loss of mature NK cells in the absence of this nuclear protein. Thus, many cell lineages of the immune system share a TOX-dependent step for development.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bone Marrow Cells / immunology
  • Cell Differentiation / genetics
  • Cell Lineage / genetics
  • Cells, Cultured
  • High Mobility Group Proteins / genetics
  • High Mobility Group Proteins / immunology*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / physiology*
  • Killer Cells, Natural / immunology*
  • Lymphoid Tissue / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • T-Lymphocytes, Helper-Inducer / immunology*


  • High Mobility Group Proteins
  • Homeodomain Proteins
  • Rhox8 protein, mouse