IL-7 promotes Glut1 trafficking and glucose uptake via STAT5-mediated activation of Akt to support T-cell survival
Open Access
- 15 February 2008
- journal article
- Published by American Society of Hematology in Blood
- Vol. 111 (4), 2101-2111
- https://doi.org/10.1182/blood-2007-06-096297
Abstract
Lymphocyte homeostasis requires coordination of metabolic processes with cellular energetic and biosynthetic demands but mechanisms that regulate T-cell metabolism are uncertain. We show that interleukin-7 (IL-7) is a key regulator of glucose uptake in T lymphocytes. To determine how IL-7 affects glucose uptake, we analyzed IL-7 signaling mechanisms and regulation of the glucose transporter, Glut1. The IL-7 receptor (IL-7R) stimulated glucose uptake and cell-surface localization of Glut1 in a manner that required IL-7R Y449, which promoted rapid signal transducer and activator of transcription 5 (STAT5) activation and a delayed yet sustained activation of Akt. Each pathway was necessary for IL-7 to promote glucose uptake, as Akt1−/− T cells or PI3-kinase inhibition and RNAi of STAT5 led to defective glucose uptake in response to IL-7. STAT5 and Akt acted in a linear pathway, with STAT5-mediated transcription leading to Akt activation, which was necessary for STAT5 and IL-7 to promote glucose uptake and prevent cell death. Importantly, IL-7 required glucose uptake to promote cell survival. These data demonstrate that IL-7 promotes glucose uptake via a novel signaling mechanism in which STAT5 transcriptional activity promotes Akt activation to regulate Glut1 trafficking and glucose uptake that is critical for IL-7 to prevent T-cell death and maintain homeostasis.Keywords
This publication has 48 references indexed in Scilit:
- Akt1 and Akt2 are required for αβ thymocyte survival and differentiationProceedings of the National Academy of Sciences of the United States of America, 2007
- Glycogen Synthase Kinase 3α and 3β Mediate a Glucose-Sensitive Antiapoptotic Signaling Pathway To Stabilize Mcl-1Molecular and Cellular Biology, 2007
- Cytokine Stimulation Promotes Glucose Uptake via Phosphatidylinositol-3 Kinase/Akt Regulation of Glut1 Activity and TraffickingMolecular Biology of the Cell, 2007
- Impaired CD8 T cell memory and CD4 T cell primary responses in IL-7Rα mutant miceThe Journal of Experimental Medicine, 2007
- Isoform-specific requirement for Akt1 in the developmental regulation of cellular metabolism during lactationCell Metabolism, 2006
- IL-7–induced proliferation of recent thymic emigrants requires activation of the PI3K pathwayBlood, 2006
- Interleukin-3-mediated Cell Survival Signals Include Phosphatidylinositol 3-Kinase-dependent Translocation of the Glucose Transporter GLUT1 to the Cell SurfaceOnline Journal of Public Health Informatics, 2003
- Bax Deficiency Partially Corrects Interleukin-7 Receptor α DeficiencyImmunity, 2002
- Akt Maintains Cell Size and Survival by Increasing mTOR-dependent Nutrient UptakeMolecular Biology of the Cell, 2002
- JAK3 Janus kinase is involved in interleukin 7 signal pathwayFEBS Letters, 1994