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

NJ MacIver, SR Jacobs, HL Wieman… - Journal of Leucocyte …, 2008 - academic.oup.com
NJ MacIver, SR Jacobs, HL Wieman, JA Wofford, JL Coloff, JC Rathmell
Journal of Leucocyte Biology, 2008academic.oup.com
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 …
Abstract
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.
Oxford University Press