Glucose metabolism in lymphocytes is a regulated process with significant effects on immune cell function and survival

被引:376
作者
MacIver, Nancie J. [2 ]
Jacobs, Sarah R. [1 ,4 ]
Wieman, Heather L. [1 ,4 ]
Wofford, Jessica A. [1 ,4 ]
Coloff, Jonathan L. [1 ,4 ]
Rathmell, Jeffrey C. [1 ,3 ,4 ]
机构
[1] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA
[2] Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA
[3] Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA
[4] Duke Univ, Med Ctr, Sarah W Stedman Ctr Nutr & Metab, Durham, NC 27710 USA
关键词
aerobic glycolysis; Glut1; Akt; IL-7; CD28;
D O I
10.1189/jlb.0108024
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Lymphocytes require glucose uptake and metabolism for normal survival and function. The signals that regulate the expression and localization of glucose transporter 1 (Glut1) to allow glucose uptake in T cells are now beginning to be understood. Resting T cells require extracellular signals, such as cytokines, hormones, and growth factors, or low-level TCR stimulation to take up adequate glucose to maintain housekeeping functions. In the absence of extrinsic signals, resting T cells internalize and degrade Glut1 and cannot maintain viability. Activated T cells have dramatically increased metabolic requirements to support the energy and biosynthetic needs necessary for growth, proliferation, and effector function. In particular, glucose metabolism and aerobic glycolysis fuel this demand. Therefore, activation of T cells causes a large increase in Glut1 expression and surface localization. If glucose uptake is limited, glycolytic flux decreases to a level that no longer sustains viability, and proapoptotic Bcl-2 family members become activated, promoting cell death. However, excessive glucose uptake can promote hyperactive immune responses and possible immune pathology. Tight regulation of glucose uptake is required to maintain immune homeostasis, and understanding of these metabolic pathways may lead to therapeutic strategies to target some forms of cancer or autoimmunity.
引用
收藏
页码:949 / 957
页数:9
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