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Leptin metabolically licenses T cells for activation to link nutrition and immunity.

dc.contributor.author Gerriets, VA
dc.contributor.author MacIver, Nancie Jo
dc.contributor.author Rathmell, Jeffrey C
dc.contributor.author Saucillo, DC
dc.contributor.author Sheng, J
dc.coverage.spatial United States
dc.date.accessioned 2015-07-16T18:56:49Z
dc.date.issued 2014-01-01
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/24273001
dc.identifier jimmunol.1301158
dc.identifier.uri https://hdl.handle.net/10161/10314
dc.description.abstract Immune responses are highly energy-dependent processes. Activated T cells increase glucose uptake and aerobic glycolysis to survive and function. Malnutrition and starvation limit nutrients and are associated with immune deficiency and increased susceptibility to infection. Although it is clear that immunity is suppressed in times of nutrient stress, mechanisms that link systemic nutrition to T cell function are poorly understood. We show in this study that fasting leads to persistent defects in T cell activation and metabolism, as T cells from fasted animals had low glucose uptake and decreased ability to produce inflammatory cytokines, even when stimulated in nutrient-rich media. To explore the mechanism of this long-lasting T cell metabolic defect, we examined leptin, an adipokine reduced in fasting that regulates systemic metabolism and promotes effector T cell function. We show that leptin is essential for activated T cells to upregulate glucose uptake and metabolism. This effect was cell intrinsic and specific to activated effector T cells, as naive T cells and regulatory T cells did not require leptin for metabolic regulation. Importantly, either leptin addition to cultured T cells from fasted animals or leptin injections to fasting animals was sufficient to rescue both T cell metabolic and functional defects. Leptin-mediated metabolic regulation was critical, as transgenic expression of the glucose transporter Glut1 rescued cytokine production of T cells from fasted mice. Together, these data demonstrate that induction of T cell metabolism upon activation is dependent on systemic nutritional status, and leptin links adipocytes to metabolically license activated T cells in states of nutritional sufficiency.
dc.language eng
dc.relation.ispartof J Immunol
dc.relation.isversionof 10.4049/jimmunol.1301158
dc.subject Animals
dc.subject Cytokines
dc.subject Fasting
dc.subject Glucose
dc.subject Glucose Transporter Type 1
dc.subject Glycolysis
dc.subject Inflammation Mediators
dc.subject Leptin
dc.subject Lymphocyte Activation
dc.subject Mice
dc.subject Mice, Knockout
dc.subject Mitochondria
dc.subject Receptors, Leptin
dc.subject T-Lymphocyte Subsets
dc.title Leptin metabolically licenses T cells for activation to link nutrition and immunity.
dc.type Journal article
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/24273001
pubs.begin-page 136
pubs.end-page 144
pubs.issue 1
pubs.organisational-group Basic Science Departments
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Molecular Physiology Institute
pubs.organisational-group Immunology
pubs.organisational-group Institutes and Centers
pubs.organisational-group Pediatrics
pubs.organisational-group Pediatrics, Endocrinology
pubs.organisational-group Pharmacology & Cancer Biology
pubs.organisational-group Sarah Stedman Nutrition & Metabolism Center
pubs.organisational-group School of Medicine
pubs.publication-status Published
pubs.volume 192
dc.identifier.eissn 1550-6606


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