IL-7-Induced Glycerol Transport and TAG Synthesis Promotes Memory CD8+ T Cell Longevity

Cui, Guoliang; Staron, Matthew; Gray, Simon M.; Ho, Ping‐Chih; Amezquita, Robert A.; Wu, Jingxia; Kaech, Susan M.

doi:10.1016/j.cell.2015.03.021

Cited by 276 publications

(246 citation statements)

References 52 publications

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“…In fact, T cells take up and store high levels of metabolites during T cell priming, such as amino acids, lipids, and nucleotides (65), and these may serve as an immediate source of energy upon T cell activation. When in a resting state, IL-7R signaling mediates the synthesis and storage of fatty acids in memory T cells, which promote T cell survival and a fast response to secondary infections (66,67). Memory T cells also display a substantial mitochondrial mass (42), thereby exhibiting a greater capacity to use both OXPHOS and glycolysis to generate ATP.…”

Section: Discussionmentioning

confidence: 99%

TLR-Mediated Innate Production of IFN-γ by CD8+ T Cells Is Independent of Glycolysis

Salerno

Guislain

Cansever

et al. 2016

The Journal of Immunology

120

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CD8+ T cells can respond to unrelated infections in an Ag-independent manner. This rapid innate-like immune response allows Ag-experienced T cells to alert other immune cell types to pathogenic intruders. In this study, we show that murine CD8+ T cells can sense TLR2 and TLR7 ligands, resulting in rapid production of IFN-γ but not of TNF-α and IL-2. Importantly, Ag-experienced T cells activated by TLR ligands produce sufficient IFN-γ to augment the activation of macrophages. In contrast to Ag-specific reactivation, TLR-dependent production of IFN-γ by CD8+ T cells relies exclusively on newly synthesized transcripts without inducing mRNA stability. Furthermore, transcription of IFN-γ upon TLR triggering depends on the activation of PI3K and serine-threonine kinase Akt, and protein synthesis relies on the activation of the mechanistic target of rapamycin. We next investigated which energy source drives the TLR-induced production of IFN-γ. Although Ag-specific cytokine production requires a glycolytic switch for optimal cytokine release, glucose availability does not alter the rate of IFN-γ production upon TLR-mediated activation. Rather, mitochondrial respiration provides sufficient energy for TLR-induced IFN-γ production. To our knowledge, this is the first report describing that TLR-mediated bystander activation elicits a helper phenotype of CD8+ T cells. It induces a short boost of IFN-γ production that leads to a significant but limited activation of Ag-experienced CD8+ T cells. This activation suffices to prime macrophages but keeps T cell responses limited to unrelated infections.

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Section: Discussionmentioning

confidence: 99%

TLR-Mediated Innate Production of IFN-γ by CD8+ T Cells Is Independent of Glycolysis

Salerno

Guislain

Cansever

et al. 2016

The Journal of Immunology

120

View full text Add to dashboard Cite

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“…There are a number of studies that also support the notion that promoting OxPhos enhances cell survival and life span (10)(11)(12). Memory T cells use glucose and other fuels to synthesize an energy store in the form of triglycerides, which are then broken down by FAO, to fuel ATP synthesis (13,14). In this way, these cells maintain both glycolysis and OxPhos primed and ready for immune activation, allowing memory T cells to initiate a metabolic response much quicker than naive T cells (15,16).…”

Section: Oxphos Facilitates Cellular Longevitymentioning

confidence: 95%

Metabolic regulation of immune responses: therapeutic opportunities

Aßmann¹,

Finlay²

2016

Journal of Clinical Investigation

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“…The clonal expansion and differentiation into effector CD8 ϩ T cells seems to be antigen driven (7,222). After pathogen clearance, the majority of the effector CD8 ϩ T cells die and a small population of CD8 ϩ T cells survives as memory T cells (51,283). Upon antigen resensitization, resident memory CD8 ϩ T cells secrete cytokines that trigger rapid adaptive and innate immune responses.…”

Section: Recruitment Of Proinflammatory Immune Cells In Obesity Perpementioning

confidence: 99%

Revisiting the adipocyte: a model for integration of cytokine signaling in the regulation of energy metabolism

Rodrı́guez

Ezquerro

Méndez‐Giménez

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

241

186

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Adipose tissue constitutes an extremely active endocrine organ with a network of signaling pathways enabling the organism to adapt to a wide range of different metabolic challenges, such as starvation, stress, infection, and short periods of gross energy excess. The functional pleiotropism of adipose tissue relies on its ability to synthesize and release a huge variety of hormones, cytokines, complement and growth factors, extracellular matrix proteins, and vasoactive factors, collectively termed adipokines. Obesity is associated with adipose tissue dysfunction leading to the onset of several pathologies including type 2 diabetes, dyslipidemia, nonalcoholic fatty liver, or hypertension, among others. The mechanisms underlying the development of obesity and its associated comorbidities include the hypertrophy and/or hyperplasia of adipocytes, adipose tissue inflammation, impaired extracellular matrix remodeling, and fibrosis together with an altered secretion of adipokines. Recently, the potential role of brown and beige adipose tissue in the protection against obesity has been also recognized. In contrast to white adipocytes, which store energy in the form of fat, brown and beige fat cells display energy-dissipating capacity through the promotion of triacylglycerol clearance, glucose disposal, and generation of heat for thermogenesis. Identification of the morphological and molecular changes in white, beige, and brown adipose tissue during weight gain is of utmost relevance for the identification of pharmacological targets for the treatment of obesity and its associated metabolic diseases. white and brown adipogenesis; fat browning; adipocyte hypertrophy and hyperplasia; adipose tissue inflammation; extracellular matrix remodeling THE ADIPOSE ORGAN REPRESENTS a special loose connective tissue containing adipocytes and several cell types surrounded by capillary and innervation networks (47, 79, 82). Adipocytes comprise ϳ35-70% of adipose mass, and the other cell types found in the stroma-vascular fraction include preadipocytes, mesenchymal stem cells, macrophages and other immune cells, and endothelial and smooth muscle cells, among others (79). The classical functions of adipose tissue are the storage of energy in the form of triacylglycerols (TG) and as thermal insulator. Adipocytes were formerly classified into two main types: white adipocytes, which store energy in the form of fat, and brown adipocytes, which induce thermogenesis (82). The current classification scheme includes a third category of adipocytes, termed beige or brite (brown-in-white) adipocytes, which can be considered inducible brown-like cells with thermogenic properties (340). Since the identification of leptin in 1994 (359), adipose tissue has emerged as an extremely active endocrine organ that secretes a huge variety of hormones, cytokines, growth factors, and vasoactive factors that are collectively termed adipokines (67, 81,235,262). Over the last three decades, overwhelming evidence has proven that adipokines not only influence adipobiol...

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IL-7-Induced Glycerol Transport and TAG Synthesis Promotes Memory CD8+ T Cell Longevity

Cited by 276 publications

References 52 publications

TLR-Mediated Innate Production of IFN-γ by CD8+ T Cells Is Independent of Glycolysis

TLR-Mediated Innate Production of IFN-γ by CD8+ T Cells Is Independent of Glycolysis

Metabolic regulation of immune responses: therapeutic opportunities

Revisiting the adipocyte: a model for integration of cytokine signaling in the regulation of energy metabolism

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