Natural Killer Cell Education Is Associated With a Distinct Glycolytic Profile
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Natural Killer Cell Education Is Associated With a Distinct Glycolytic Profile. / Pfeifer, Caroline; Highton, Andrew J; Peine, Sven; Sauter, Jürgen; Schmidt, Alexander H; Bunders, Madeleine J; Altfeld, Marcus; Körner, Christian.
In: FRONT IMMUNOL, Vol. 9, 2018, p. 3020.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Natural Killer Cell Education Is Associated With a Distinct Glycolytic Profile
AU - Pfeifer, Caroline
AU - Highton, Andrew J
AU - Peine, Sven
AU - Sauter, Jürgen
AU - Schmidt, Alexander H
AU - Bunders, Madeleine J
AU - Altfeld, Marcus
AU - Körner, Christian
PY - 2018
Y1 - 2018
N2 - NK cells expressing self-inhibitory receptors display increased functionality compared to NK cells lacking those receptors. The acquisition of functional competence in these particular NK-cell subsets is termed education. Little is known about the underlying mechanisms that lead to the functional differences between educated and uneducated NK cells. An increasing number of studies suggest that cellular metabolism is a determinant of immune cell functions. Thus, alterations in cellular metabolic pathways may play a role in the process of NK-cell education. Here, we compared the glycolytic profile of educated and uneducated primary human NK cells. KIR-educated NK cells showed significantly increased expression levels of the glucose transporter Glut1 in comparison to NKG2A-educated or uneducated NK cells with and without exposure to target cells. Subsequently, the metabolic profile of NK-cell subsets was determined using a Seahorse XF Analyzer. Educated NK cells displayed significantly higher rates of cellular glycolysis than uneducated NK cells even in a resting state. Our results indicate that educated and uneducated NK cells reside in different metabolic states prior to activation. These differences in the ability to utilize glucose may represent an underlying mechanism for the superior functionality of educated NK cells expressing self-inhibitory receptors.
AB - NK cells expressing self-inhibitory receptors display increased functionality compared to NK cells lacking those receptors. The acquisition of functional competence in these particular NK-cell subsets is termed education. Little is known about the underlying mechanisms that lead to the functional differences between educated and uneducated NK cells. An increasing number of studies suggest that cellular metabolism is a determinant of immune cell functions. Thus, alterations in cellular metabolic pathways may play a role in the process of NK-cell education. Here, we compared the glycolytic profile of educated and uneducated primary human NK cells. KIR-educated NK cells showed significantly increased expression levels of the glucose transporter Glut1 in comparison to NKG2A-educated or uneducated NK cells with and without exposure to target cells. Subsequently, the metabolic profile of NK-cell subsets was determined using a Seahorse XF Analyzer. Educated NK cells displayed significantly higher rates of cellular glycolysis than uneducated NK cells even in a resting state. Our results indicate that educated and uneducated NK cells reside in different metabolic states prior to activation. These differences in the ability to utilize glucose may represent an underlying mechanism for the superior functionality of educated NK cells expressing self-inhibitory receptors.
KW - Cell Line
KW - Glucose Transporter Type 1/metabolism
KW - Glycolysis/immunology
KW - Healthy Volunteers
KW - Humans
KW - Immunomagnetic Separation
KW - Killer Cells, Natural/immunology
KW - NK Cell Lectin-Like Receptor Subfamily C/immunology
KW - Primary Cell Culture
U2 - 10.3389/fimmu.2018.03020
DO - 10.3389/fimmu.2018.03020
M3 - SCORING: Journal article
C2 - 30619362
VL - 9
SP - 3020
JO - FRONT IMMUNOL
JF - FRONT IMMUNOL
SN - 1664-3224
ER -