TOX regulates the differentiation of human natural killer cells from hematopoietic stem cells in vitro

Immunol Lett. 2011 Apr 30;136(1):29-36. doi: 10.1016/j.imlet.2010.11.008. Epub 2010 Nov 30.


Natural killer (NK) cells act important roles in innate immunity and adaptive immunity. However, the mechanisms governing NK cell development have not been clearly elucidated. Previous studies have shown that an HMG (high-mobility group) protein, TOX, is important for regulating the differentiation program of developing T cells in mice. In this study, we examined the role of TOX in differentiation of human NK cells. Knockdown of TOX in differentiating cells decreased the NK cell population identified by expression of NK surface markers and receptors. In addition, over-expression of TOX enhanced the differentiation of NK cells which give rise to a population showing effector functions of mature NK cells. Moreover, TOX influenced expression of T-bet (T-box expressed in T cells, also as known as Tbx21) during NK cell development. Overall, these results suggest that TOX is required for IL-15-mediated NK cell differentiation and affected expression of T-bet that plays critical roles in NK differentiation and maturation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation*
  • Gene Expression Regulation
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / immunology*
  • High Mobility Group Proteins / genetics
  • High Mobility Group Proteins / immunology*
  • Humans
  • K562 Cells
  • Killer Cells, Natural / cytology*
  • Killer Cells, Natural / immunology*
  • RNA, Small Interfering / genetics
  • Transcription, Genetic


  • High Mobility Group Proteins
  • RNA, Small Interfering
  • TOX protein, human