TY - JOUR
T1 - Crk adaptor proteins regulate nk cell expansion and differentiation during mouse cytomegalovirus infection
AU - Nabekura, Tsukasa
AU - Chen, Zhiying
AU - Schroeder, Casey
AU - Park, Taeju
AU - Vivier, Eric
AU - Lanier, Lewis L.
AU - Liu, Dongfang
N1 - Publisher Copyright:
Copyright 2018 by The American Association of Immunologists, Inc.
PY - 2018/5/15
Y1 - 2018/5/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85047055699&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85047055699&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1701639
DO - 10.4049/jimmunol.1701639
M3 - Article
C2 - 29618525
AN - SCOPUS:85047055699
SN - 0022-1767
VL - 200
SP - 3420
EP - 3428
JO - Journal of Immunology
JF - Journal of Immunology
IS - 10
ER -