Costimulatory Molecule DNAM-1 Is Essential for Optimal Differentiation of Memory Natural Killer Cells during Mouse Cytomegalovirus Infection

Tsukasa Nabekura; Minoru Kanaya; Akira Shibuya; Guo Fu; Nicholas R.J. Gascoigne; Lewis L. Lanier

doi:10.1016/j.immuni.2013.12.011

Costimulatory Molecule DNAM-1 Is Essential for Optimal Differentiation of Memory Natural Killer Cells during Mouse Cytomegalovirus Infection

Tsukasa Nabekura
, Minoru Kanaya
, Akira Shibuya
, Guo Fu
, Nicholas R.J. Gascoigne
, Lewis L. Lanier

Research output: Contribution to journal › Article › peer-review

161 Scopus citations

Abstract

Recent studies demonstrate that natural killer (NK) cells have adaptive immune features. Here, we investigated the role of the costimulatory molecule DNAM-1 in the differentiation of NK cells in a mouse model of cytomegalovirus (MCMV) infection. Antibody blockade of DNAM-1 suppressed the expansion of MCMV-specific Ly49H⁺ cells during viral infection and inhibited the generation of memory NK cells. Similarly, DNAM-1-deficient (Cd226^-/-) Ly49H⁺ NK cells exhibited intrinsic defects in expansion and differentiation into memory cells. Src-family tyrosine kinase Fyn and serine-threonine protein kinase C isoform eta (PKCη) signaling through DNAM-1 played distinct roles in the generation of MCMV-specific effector and memory NK cells. Thus, cooperative signaling through DNAM-1 and Ly49H are required for NK cell-mediated host defense against MCMV infection.

Original language	English (US)
Pages (from-to)	225-234
Number of pages	10
Journal	Immunity
Volume	40
Issue number	2
DOIs	https://doi.org/10.1016/j.immuni.2013.12.011
State	Published - Feb 20 2014
Externally published	Yes

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.immuni.2013.12.011

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title = "Costimulatory Molecule DNAM-1 Is Essential for Optimal Differentiation of Memory Natural Killer Cells during Mouse Cytomegalovirus Infection",

abstract = "Recent studies demonstrate that natural killer (NK) cells have adaptive immune features. Here, we investigated the role of the costimulatory molecule DNAM-1 in the differentiation of NK cells in a mouse model of cytomegalovirus (MCMV) infection. Antibody blockade of DNAM-1 suppressed the expansion of MCMV-specific Ly49H+ cells during viral infection and inhibited the generation of memory NK cells. Similarly, DNAM-1-deficient (Cd226-/-) Ly49H+ NK cells exhibited intrinsic defects in expansion and differentiation into memory cells. Src-family tyrosine kinase Fyn and serine-threonine protein kinase C isoform eta (PKCη) signaling through DNAM-1 played distinct roles in the generation of MCMV-specific effector and memory NK cells. Thus, cooperative signaling through DNAM-1 and Ly49H are required for NK cell-mediated host defense against MCMV infection.",

author = "Tsukasa Nabekura and Minoru Kanaya and Akira Shibuya and Guo Fu and Gascoigne, \{Nicholas R.J.\} and Lanier, \{Lewis L.\}",

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doi = "10.1016/j.immuni.2013.12.011",

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AU - Nabekura, Tsukasa

AU - Kanaya, Minoru

AU - Shibuya, Akira

AU - Fu, Guo

AU - Gascoigne, Nicholas R.J.

AU - Lanier, Lewis L.

PY - 2014/2/20

Y1 - 2014/2/20

N2 - Recent studies demonstrate that natural killer (NK) cells have adaptive immune features. Here, we investigated the role of the costimulatory molecule DNAM-1 in the differentiation of NK cells in a mouse model of cytomegalovirus (MCMV) infection. Antibody blockade of DNAM-1 suppressed the expansion of MCMV-specific Ly49H+ cells during viral infection and inhibited the generation of memory NK cells. Similarly, DNAM-1-deficient (Cd226-/-) Ly49H+ NK cells exhibited intrinsic defects in expansion and differentiation into memory cells. Src-family tyrosine kinase Fyn and serine-threonine protein kinase C isoform eta (PKCη) signaling through DNAM-1 played distinct roles in the generation of MCMV-specific effector and memory NK cells. Thus, cooperative signaling through DNAM-1 and Ly49H are required for NK cell-mediated host defense against MCMV infection.

AB - Recent studies demonstrate that natural killer (NK) cells have adaptive immune features. Here, we investigated the role of the costimulatory molecule DNAM-1 in the differentiation of NK cells in a mouse model of cytomegalovirus (MCMV) infection. Antibody blockade of DNAM-1 suppressed the expansion of MCMV-specific Ly49H+ cells during viral infection and inhibited the generation of memory NK cells. Similarly, DNAM-1-deficient (Cd226-/-) Ly49H+ NK cells exhibited intrinsic defects in expansion and differentiation into memory cells. Src-family tyrosine kinase Fyn and serine-threonine protein kinase C isoform eta (PKCη) signaling through DNAM-1 played distinct roles in the generation of MCMV-specific effector and memory NK cells. Thus, cooperative signaling through DNAM-1 and Ly49H are required for NK cell-mediated host defense against MCMV infection.

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Costimulatory Molecule DNAM-1 Is Essential for Optimal Differentiation of Memory Natural Killer Cells during Mouse Cytomegalovirus Infection

Abstract

ASJC Scopus subject areas

UN SDGs

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