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

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

Author information

1
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143.
2
Parker Institute for Cancer Immunotherapy, San Francisco, CA 94143.
3
Life Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki 305-8577, Japan.
4
Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030.
5
Children's Research Institute, Children's Mercy Kansas City, Kansas City, MO 64108.
6
Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, 13288 Marseille, France.
7
Service d'Immunologie, Hôpital de la Timone, Assistance Publique-Hôpitaux de Marseille, 13288 Marseille, France; and.
8
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143; Lewis.Lanier@ucsf.edu dliu2@houstonmethodist.org.
9
Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030; Lewis.Lanier@ucsf.edu dliu2@houstonmethodist.org.
10
Department of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, New York, NY 10065.

Abstract

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.

PMID:
29618525
PMCID:
PMC5940538
[Available on 2019-05-15]
DOI:
10.4049/jimmunol.1701639

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