Crk Adaptor Proteins Regulate NK Cell Expansion and Differentiation during Mouse Cytomegalovirus Infection

J Immunol. 2018 May 15;200(10):3420-3428. doi: 10.4049/jimmunol.1701639. Epub 2018 Apr 4.


Natural killer cells are critical in the immune response to infection and malignancy. Prior studies have demonstrated that Crk family proteins can influence cell apoptosis, proliferation, and cell transformation. In this study, we investigated the role of Crk family proteins in mouse NK cell differentiation and host defense using a mouse CMV infection model. The number of NK cells, maturational state, and the majority of the NKR repertoire was similar in Crk x Crk-like (CrkL)-double-deficient and wild type NK cells. However, Crk family proteins were required for optimal activation, IFN-γ production, expansion, and differentiation of Ly49H+ NK cells, as well as host defense during mouse CMV infection. The diminished function of Crk x CrkL-double-deficient NK cells correlated with decreased phosphorylation of STAT4 and STAT1 in response to IL-12 and IFN-α stimulation, respectively. Together, our findings analyzing NK cell-specific Crk-deficient mice provide insights into the role of Crk family proteins in NK cell function and host defense.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / immunology
  • Cell Differentiation / physiology*
  • Cell Proliferation / physiology
  • Cytomegalovirus Infections / immunology
  • Cytomegalovirus Infections / metabolism*
  • Cytomegalovirus Infections / virology
  • Interferon-alpha / metabolism
  • Interleukin-12 / metabolism
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism*
  • Killer Cells, Natural / virology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muromegalovirus / immunology*
  • NK Cell Lectin-Like Receptor Subfamily A / metabolism
  • Proto-Oncogene Proteins c-crk / metabolism*
  • STAT1 Transcription Factor / metabolism
  • STAT4 Transcription Factor / metabolism
  • Signal Transduction / immunology
  • Signal Transduction / physiology


  • Crk protein, mouse
  • Interferon-alpha
  • NK Cell Lectin-Like Receptor Subfamily A
  • Proto-Oncogene Proteins c-crk
  • STAT1 Transcription Factor
  • STAT4 Transcription Factor
  • Interleukin-12