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 - Funding Information:
This work was supported in part by National Heart, Lung, and Blood Institute/ National Institutes of Health Grant HL125018 and National Institute of Allergy and Infectious Diseases/National Institutes of Health Grants AI124769, AI129594, and AI130197 (all to D.L.) and AI068129 (to L.L.L.), a Houston Methodist Career Cornerstone Award (to D.L.), Baylor–University of Texas Houston Center for AIDS Research Core Support Grant AI036211 from the National Institute of Allergy and Infectious Diseases (to D.L.), a Houston Methodist Research Institute for Academic Medicine National Institutes of Health Competitiveness Initiative Award (to D.L.), the Caroline Weiss Law Fund for Research in Molecular Medicine (to D.L.), the Texas Children’s Hospital Pediatrics Pilot Research Fund (to D.L.), and the Lymphoma Specialized Program of Research Excellence Developmental Research Program from Baylor College of Medicine and the Methodist Research Institute (P50 CA126752). L.L.L. is an American Cancer Society professor and is funded in part by the Parker Institute for Cancer Immunotherapy. T.N. is supported by the Friends of Leukemia Research Fund and the Nakajima Foundation. The laboratory of E.V. is supported by the European Research Council (ERC-2015-AdG - 694502_TILC), the Ligue Nationale contre le Cancer (Equipe Labellisée), Innate-Pharma, MSDAvenir, and by institutional grants from INSERM, CNRS, Aix-Marseille University, and Marseille Immunopole to Centre d’Immunologie de Marseille-Luminy. 10.4049/jimmunol.1701639 We thank Dr. Marco Colonna (Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO) for transferring NKp46-iCre mice to the laboratory of Dr. Dongfang Liu. We thank Dr. Yan Yang for critical reading of the manuscript. We thank Dr. Rongfu Wang and Dr. Changsheng Xing (Houston Methodist Research Institute) for providing reagents.
Funding Information:
This work was supported in part by National Heart, Lung, and Blood Institute/ National Institutes of Health Grant HL125018 and National Institute of Allergy and Infectious Diseases/National Institutes of Health Grants AI124769, AI129594, and AI130197 (all to D.L.) and AI068129 (to L.L.L.), a Houston Methodist Career Cornerstone Award (to D.L.), Baylor?University of Texas Houston Center for AIDS Research Core Support Grant AI036211 from the National Institute of Allergy and Infectious Diseases (to D.L.), a Houston Methodist Research Institute for Academic Medicine National Institutes of Health Competitiveness Initiative Award (to D.L.), the Caroline Weiss Law Fund for Research in Molecular Medicine (to D.L.), the Texas Children?s Hospital Pediatrics Pilot Research Fund (to D.L.), and the Lymphoma Specialized Program of Research Excellence Developmental Research Program from Baylor College of Medicine and the Methodist Research Institute (P50 CA126752). L.L.L. is an American Cancer Society professor and is funded in part by the Parker Institute for Cancer Immunotherapy. T.N. is supported by the Friends of Leukemia Research Fund and the Nakajima Foundation. The laboratory of E.V. is supported by the European Research Council (ERC-2015-AdG - 694502_TILC), the Ligue Nationale contre le Cancer (Equipe Labellis?e), Innate-Pharma, MSDAvenir, and by institutional grants from INSERM, CNRS, Aix-Marseille University, and Marseille Immunopole to Centre d?Immunologie de Marseille-Luminy. 10.4049/jimmunol.1701639 We thank Dr. Marco Colonna (Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO) for transferring NKp46-iCre mice to the laboratory of Dr. Dongfang Liu. We thank Dr. Yan Yang for critical reading of the manuscript. We thank Dr. Rongfu Wang and Dr. Changsheng Xing (Houston Methodist Research Institute) for providing reagents.
Publisher Copyright:
Copyright 2018 by The American Association of Immunologists, Inc.
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
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-g 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-a 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-g 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-a 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.
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U2 - 10.4049/jimmunol.1701639
DO - 10.4049/jimmunol.1701639
M3 - Article
AN - SCOPUS:85047055699
VL - 200
SP - 3420
EP - 3428
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 10
ER -