PDK1 regulation of mTOR and hypoxia-inducible factor 1 integrate metabolism and migration of CD8+ T cells

A PI3K- and Akt-independent pathway mediated by mTORC1 regulates expression of HIF1 in CD8+ T cells and is required to sustain glucose metabolism and regulate cell trafficking.

• Publication year

  2012

• Venue

  Journal of Experimental Medicine

• Publication date

  2012-12-10

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1084/jem.20112607PMID 23183047PMCID 3526360
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Characterization of MRFAP1 Turnover and Interactions Downstream of the NEDD8 Pathway

  2011cited by this paper
• Faculty Opinions recommendation of HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells.

  2011cited by this paper
• Protein Kinase B Controls Transcriptional Programs that Direct Cytotoxic T Cell Fate but Is Dispensable for T Cell Metabolism

  2011cited by this paper
• HIF1α–dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells

  2011cited by this paper
• The mammalian Target of Rapamycin (mTOR) regulates T helper cell differentiation through the selective activation of mTORC1 and mTORC2 signaling

  2011cited by this paper
• Phosphoproteomic analysis reveals an intrinsic pathway for the regulation of histone deacetylase 7 that controls the function of cytotoxic T lymphocytes

  2011cited by this paper
• The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation.

  2011influential reference
• Prolonged interleukin-2Ralpha expression on virus-specific CD8+ T cells favors terminal-effector differentiation in vivo.

  2010cited by this paper
• Mammalian target of rapamycin protein complex 2 regulates differentiation of Th1 and Th2 cell subsets via distinct signaling pathways.

  2010cited by this paper
• HIF-1: upstream and downstream of cancer metabolism.

  2010cited by this paper
• The mTOR kinase determines effector versus memory CD8+ T cell fate by regulating the expression of transcription factors T-bet and Eomesodermin.

  2010cited by this paper
• Interleukin-2 and inflammation induce distinct transcriptional programs that promote the differentiation of effector cytolytic T cells.

  2010cited by this paper
• The mammalian target of rapamycin: linking T cell differentiation, function, and metabolism.

  2010cited by this paper
• Foxo1 links homing and survival of naive T cells by regulating L-selectin, CCR7 and interleukin 7 receptor

  2009cited by this paper
• mTOR regulates memory CD8 T cell differentiation

  2009cited by this paper
• Phosphoinositide (3,4,5)-Triphosphate Binding to Phosphoinositide-Dependent Kinase 1 Regulates a Protein Kinase B/Akt Signaling Threshold That Dictates T-Cell Migration, Not Proliferation

  2009influential reference
• Runx3 and T-box proteins cooperate to establish the transcriptional program of effector CTLs

  2009cited by this paper
• Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources

  2008cited by this paper
• MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification

  2008cited by this paper
• Phosphatidylinositol-3-OH kinase and nutrient-sensing mTOR pathways control T lymphocyte trafficking

  2008influential reference
• Glucose metabolism in lymphocytes is a regulated process with significant effects on immune cell function and survival

  2008cited by this paper
• Glucose deprivation inhibits multiple key gene expression events and effector functions in CD8+ T cells

  2008influential reference
• Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists

  2008cited by this paper
• FOXO1 Regulates L-Selectin and a Network of Human T Cell Homing Molecules Downstream of Phosphatidylinositol 3-Kinase1

  2008cited by this paper
• Targeted ablation of Arnt in mouse epidermis results in profound defects in desquamation and epidermal barrier function

  2006cited by this paper
• Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB.

  2006influential reference
• Glucose Availability Regulates IFN-γ Production and p70S6 Kinase Activation in CD8+ Effector T Cells1

  2005cited by this paper
• Fuel feeds function: energy metabolism and the T-cell response

  2005cited by this paper
• Deficiency of PDK1 in cardiac muscle results in heart failure and increased sensitivity to hypoxia

  2003cited by this paper
• Impaired B and T Cell Antigen Receptor Signaling in p110δ PI 3-Kinase Mutant Mice

  2002cited by this paper
• Differential Effects of Physiologically Relevant Hypoxic Conditions on T Lymphocyte Development and Effector Functions

  2001cited by this paper
• Direct inhibition of the signaling functions of the mammalian target of rapamycin by the phosphoinositide 3‐kinase inhibitors, wortmannin and LY294002.

  1996cited by this paper
• Constitutive class I-restricted exogenous presentation of self antigens in vivo

  1996cited by this paper
• Cell surface labeling of glucose transporter isoform GLUT4 by bis-mannose photolabel. Correlation with stimulation of glucose transport in rat adipose cells by insulin and phorbol ester.

  1990cited by this paper
• Tolerance induction in double specific T-cell receptor transgenic mice varies with antigen

  1989cited by this paper
• Energy metabolism and T-cell-mediated cytolysis. I. Synergism between inhibitors of respiration and glycolysis

  1977cited by this paper
• Références

  year unknowncited by this paper

• Spatiotemporal regulation of energetic charge dictates T cell function

  2026cites this paper
• T Cell Exhaustion in Hepatocellular Carcinoma: A Substantial Barrier in Immunotherapy

  2026cites this paper
• Distinct sensing of BCAAs by mTOR and c-Myc governs T cell proliferation, independent of catabolism

  2026cites this paper
• Regulatory networks of HIFs in tumor-infiltrating immune cells: From molecular mechanisms to therapeutic implications (Review)

  2026cites this paper
• Glucose availability tunes latent CD8+ T cell expansion potential through a mitogen-independent, mTOR-dependent regulatory switch

  2026cites this paper
• Multi-omics approach to dissect the significance of lipid metabolism in helper T cell subset

  2025cites this paper
• mTOR activity and metabolic reprogramming of CD8+ T cells is impaired under hypoxia and within the multiple myeloma bone marrow

  2025cites this paper
• Deciphering the critical roles of the AMPK/mTOR signaling pathway in cancer cell metabolism (Review)

  2025cites this paper
• Oxygen and immunity to Leishmania infection

  2025cites this paper
• More TOR: The expanding role of mTOR in regulating immune responses.

  2025cites this paper
• Protein Synthesis and Metabolism in T Cells.

  2025cites this paper
• Metabolic T-cell phenotypes - from bioenergetics to function.

  2025cites this paper
• CCL26–CX3CR1 Axis Mediates a Feedback Loop between Cancer Cell and PMN-MDSCs to Promote CD8+ T Cell Exhaustion during Stomach Carcinogenesis

  2025cites this paper
• The MARK2 kinase acts as a gatekeeper of CD28-dependent co-stimulation in T cells

  2025cites this paper
• Restricting SLC7A5-mediated Leucine uptake in T cells prevents acute GVHD and maintains GVT response

  2025cites this paper
• Aging impairs CD8 T cell responses in adoptive T-cell therapy against solid tumors

  2025cites this paper
• Metabolism and Immune Suppressive Response in Liver Cancer

  2025cites this paper
• Decoding the metabolic dialogue in the tumor microenvironment: from immune suppression to precision cancer therapies

  2025cites this paper
• Hypoxia and IL-15 cooperate to induce perforin expression by CD8 T cells and promote damage to the skin in murine cutaneous leishmaniasis.

  2025cites this paper
• The opportunities and barriers for developing tumour-infiltrating lymphocyte therapy for patients with advanced genitourinary cancers.

  2025cites this paper
• HIF-1α stabilization in osteoclasts induces the expression of aerobic glycolysis-related proteins GLUT1, LDHA, and MCT4.

  2025cites this paper
• HIF-1α+ CD4 T cells coordinate a tissue resident immune cell network in the lung

  2025cites this paper
• Protection Against Type 1 Diabetes Development in Mice With 4E-BP2 Deletion

  2025cites this paper
• PIM kinase control of CD8 T cell protein synthesis and cell trafficking

  2025cites this paper
• Transcription factor IRF-5 regulates lipid metabolism and mitochondrial function in murine CD8+ T-cells during viral infection

  2025cites this paper
• Impaired natural killer cell migration in HIV-infected individuals is caused by TIGIT-mediated inhibition of HIF-1α-dependent glycolysis

  2025cites this paper
• PHD2 Deletion in CD8+ T Cells Worsens TAC-Induced Cardiac Inflammation, Heart Failure, and Pulmonary Remodeling.

  2025cites this paper
• Disruption of metabolic licensing by JAK inhibitors constrains CD8 T cell activation and effector function

  2025cites this paper
• Cytotoxic CD8+ T Cells Downregulate GPX4 to Promote Ferroptosis in Melanoma that Drives Antitumor Immunity.

  2025cites this paper
• Lactylation-related molecular subtyping reveals the immune heterogeneity and clinical characteristics in ulcerative colitis.

  2025cites this paper
• Metabolic regulation of Th17 and Treg cell balance by the mTOR signaling

  2025cites this paper
• Intestinal tissue‐resident memory T cells maintain distinct identity from circulating memory T cells after in vitro restimulation

  2024cites this paper
• Cell metabolism: Functional and phenotypic single cell approaches.

  2024cites this paper
• The effect of PDK1 in maintaining immune cell development and function.

  2024cites this paper
• Sustained AhR activity programs memory fate of early effector CD8+ T cells

  2024cites this paper
• The immune microenvironment of cancer of the uterine cervix.

  2024cites this paper
• New sights of immunometabolism and agent progress in colitis associated colorectal cancer

  2024cites this paper
• Neutrophil-mediated hypoxia drives pathogenic CD8+ T cell responses in cutaneous leishmaniasis

  2024cites this paper
• Metabolic waypoints during T cell differentiation

  2024cites this paper
• Single-cell NAD(H) levels predict clonal lymphocyte expansion dynamics

  2024cites this paper
• Glycolysis in the tumor microenvironment: a driver of cancer progression and a promising therapeutic target

  2024cites this paper
• The molecular landscape of T cell exhaustion in the tumor microenvironment and reinvigoration strategies

  2024cites this paper
• Enhanced tumor response to adoptive T cell therapy with PHD2/3-deficient CD8 T cells

  2024cites this paper
• Reciprocal regulation of mTORC1 signaling and ribosomal biosynthesis determines cell cycle progression in activated T cells

  2024cites this paper
• Hypoxia-adenosinergic regulation of B cell responses

  2024cites this paper
• How exercise shapes the anti-inflammatory environment in multiple sclerosis – a conceptual framework focusing on tryptophan-derived molecules in T cell differentiation

  2024cites this paper
• Metabolism at the crossroads of inflammation and fibrosis in chronic kidney disease

  2024cites this paper
• Targeting metabolic dysfunction of CD8 T cells and natural killer cells in cancer

  2024cites this paper
• ADAM10 modulates the efficacy of T‐cell‐mediated therapy in solid tumors

  2024cites this paper
• Human organoids with an autologous tissue-resident immune compartment

  2024cites this paper
• Pharmacologic HIF stabilization activates costimulatory receptor expression to increase antitumor efficacy of adoptive T cell therapy

  2024cites this paper
• The cellular-centered view of hypoxia tumor microenvironment: Molecular mechanisms and therapeutic interventions.

  2024cites this paper
• Advances in reprogramming of energy metabolism in tumor T cells

  2024cites this paper
• Coordinated ARP2/3 and glycolytic activities regulate the morphological and functional fitness of human CD8+ T cells.

  2024cites this paper
• Target modulation of glycolytic pathways as a new strategy for the treatment of neuroinflammatory diseases.

  2024cites this paper
• Glucose-oxygen deprivation constrains HMGCR function and Rac1 prenylation and activates the NLRP3 inflammasome in human monocytes

  2024cites this paper
• Intestinal oxygen utilisation and cellular adaptation during intestinal ischaemia–reperfusion injury

  2024cites this paper
• All Roads Lead to Interferon-γ: From Known to Untraveled Pathways in Acquired Aplastic Anemia

  2023cites this paper
• Combined Immunodeficiency Caused by a Novel Nonsense Mutation in LCK

  2023cites this paper
• PHD2 constrains antitumor CD8+ T-cell activity.

  2023cites this paper
• CD8+ T cells in brain injury and neurodegeneration

  2023cites this paper
• Immunoregulation: the interplay between metabolism and redox homeostasis

  2023cites this paper
• Genetic and pharmaceutical targeting of HIF1α allows combo-immunotherapy to boost graft vs. leukemia without exacerbation graft vs. host disease

  2023cites this paper
• Pathogenic CD8 T cell responses are driven by neutrophil-mediated hypoxia in cutaneous leishmaniasis

  2023cites this paper
• Thrombotic Alterations under Perinatal Hypoxic Conditions: HIF and Other Hypoxic Markers

  2023cites this paper
• Formate supplementation enhances anti-tumor CD8+ T cell fitness and efficacy of PD-1 blockade.

  2023cites this paper
• Reductive carboxylation epigenetically instructs T cell differentiation

  2023cites this paper
• mTOR signaling in hair follicle and hair diseases: recent progress

  2023cites this paper
• Mitochondrial dysfunction promotes the transition of precursor to terminally exhausted T cells through HIF-1α-mediated glycolytic reprogramming

  2023cites this paper
• Signaling Pathways Leading to mTOR Activation Downstream Cytokine Receptors in Lymphocytes in Health and Disease

  2023influential citation
• Sensing the oxygen and temperature in the adipose tissues – who’s sensing what?

  2023cites this paper
• A pooled Cell Painting CRISPR screening platform enables de novo inference of gene function by self-supervised deep learning

  2023cites this paper
• T-cell dysfunction by pseudohypoxia and autocrine purinergic signaling in chronic lymphocytic leukemia

  2023cites this paper
• Hierarchical transcriptional network governing heterogeneous T cell exhaustion and its implications for immune checkpoint blockade

  2023cites this paper
• Cross-talk between insulin resistance and nitrogen species in hypoxia leads to deterioration of tissue and homeostasis.

  2023cites this paper
• Identification of co-expressed gene networks promoting CD8+ T cell infiltration and having prognostic value in uveal melanoma

  2023cites this paper
• Combination therapy of HIFα inhibitors and Treg depletion strengthen the anti‐tumor immunity in mice

  2023cites this paper
• Hypoxia-inducible factors and essential hypertension: narrative review of experimental and clinical data

  2023cites this paper
• Serine Metabolic Reprogramming in Tumorigenesis, Tumor Immunity, and Clinical Treatment

  2023cites this paper
• Tumor-derived semaphorin 4A improves PD-1–blocking antibody efficacy by enhancing CD8+ T cell cytotoxicity and proliferation

  2023cites this paper
• Effects of altered glycolysis levels on CD8+ T cell activation and function

  2023cites this paper
• Pparα knockout in mice increases the Th17 development by facilitating the IKKα/RORγt and IKKα/Foxp3 complexes

  2023cites this paper
• Axes of heterogeneity in human tissue‐resident memory T cells

  2023cites this paper
• ENOX2 inhibition enhances infiltration of effector memory T-cell and mediates response to chemotherapy in immune-quiescent nasopharyngeal carcinoma

  2023cites this paper
• The inhibition of glycolysis in T cells by a Jak inhibitor ameliorates the pathogenesis of allergic contact dermatitis in mice.

  2023cites this paper
• Cell metabolism-based optimization strategy of CAR-T cell function in cancer therapy

  2023cites this paper
• Linoleic acid potentiates CD8+ T cell metabolic fitness and antitumor immunity.

  2023cites this paper
• Targeting of chimeric antigen receptor T cell metabolism to improve therapeutic outcomes

  2023cites this paper
• HIF-1α-mediated mitochondrial-glycolytic reprogramming controls the transition of precursor to terminally exhausted T cells

  2023cites this paper
• Pyruvate dehydrogenase kinase 1 regulates the function of human decidual natural killer cells

  2023cites this paper
• Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions

  2023cites this paper
• Lactate exposure shapes the metabolic and transcriptomic profile of CD8+ T cells

  2023influential citation
• The impact of microbiome dysbiosis on T cell function within the tumor microenvironment (TME)

  2023cites this paper
• Human intestinal organoids with an autologous tissue-resident immune compartment

  2023cites this paper
• GOT1 regulates CD8+ effector and memory T cell generation

  2023cites this paper
• Modulating T Cell Phenotype and Function to Treat Hypertension

  2023cites this paper
• Regulation of T Cell Activation and Metabolism by Transforming Growth Factor-Beta

  2023influential citation
• Engineering metabolism to modulate immunity.

  2023cites this paper
• Oxygen levels at the time of activation determine T cell persistence and immunotherapeutic efficacy

  2022influential citation
• Memory CD8+ T cells upregulate glycolysis and effector functions under limiting oxygen conditions

  2022cites this paper