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

Tsukasa Nabekura1,2,3, Zhiying Chen4, Casey Schroeder4

  • 1Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143.

Journal of Immunology (Baltimore, Md. : 1950)
|April 6, 2018
PubMed

Insights

Crk family proteins are essential for natural killer (NK) cell function and host defense against cytomegalovirus infection. Their absence impairs NK cell activation, cytokine production, and expansion.

Area of Science:

  • Immunology
  • Cell Biology
  • Virology

Background:

  • Natural killer (NK) cells are crucial for immunity against infections and cancer.
  • Crk family proteins are known to regulate cell apoptosis, proliferation, and transformation.

Purpose of the Study:

  • To investigate the role of Crk family proteins in mouse NK cell differentiation and host defense.
  • To analyze the impact of Crk and Crk-like (CrkL) deficiency on NK cell function during mouse cytomegalovirus (CMV) infection.

Main Methods:

  • Utilized a mouse cytomegalovirus (CMV) infection model.
  • Compared NK cell numbers, maturation, and NK receptor repertoire in Crk x Crk-like (CrkL)-double-deficient mice versus wild-type mice.
  • Assessed NK cell activation, IFN-γ production, expansion, and differentiation, as well as STAT4 and STAT1 phosphorylation.

Main Results:

  • NK cell numbers, maturational state, and NK receptor repertoire were similar between deficient and wild-type mice.
  • Crk family proteins were required for optimal activation, IFN-γ production, expansion, and differentiation of Ly49H+ NK cells.
  • Deficiency in Crk family proteins impaired host defense during mouse CMV infection.
  • Diminished NK cell function correlated with reduced STAT4 and STAT1 phosphorylation following IL-12 and IFN-α stimulation, respectively.

Conclusions:

  • Crk family proteins are critical for optimal NK cell function, including activation, cytokine production, and expansion.
  • Crk family proteins play a significant role in host defense against mouse CMV infection.
  • These findings highlight the importance of Crk family proteins in regulating NK cell-mediated immunity.

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