SHP-1-mediated inhibitory signals promote responsiveness and anti-tumour functions of natural killer cells

Nat Commun. 2014 Oct 30:5:5108. doi: 10.1038/ncomms6108.


Natural killer (NK) cells are cytotoxic innate lymphoid cells that are involved in immune defense. NK cell reactivity is controlled in part by MHC class I recognition by inhibitory receptors, but the underlying molecular mechanisms remain undefined. Using a mouse model of conditional deletion in NK cells, we show here that the protein tyrosine phosphatase SHP-1 is essential for the inhibitory function of NK cell MHC class I receptors. In the absence of SHP-1, NK cells are hyporesponsive to tumour cells in vitro and their early Ca(2+) signals are compromised. Mice without SHP-1 in NK cells are unable to reject MHC class I-deficient transplants and to control tumours in vivo. Thus, the inhibitory activity of SHP-1 is needed for setting the threshold of NK cell reactivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Female
  • Histocompatibility Antigens Class I / metabolism
  • Killer Cells, Natural / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • NK Cell Lectin-Like Receptor Subfamily A / metabolism
  • Phenotype
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6 / metabolism*


  • Histocompatibility Antigens Class I
  • NK Cell Lectin-Like Receptor Subfamily A
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Ptpn6 protein, mouse