2024
Fatty acid binding protein 5 suppression attenuates obesity-induced hepatocellular carcinoma by promoting ferroptosis and intratumoral immune rewiring
Sun J, Esplugues E, Bort A, Cardelo M, Ruz-Maldonado I, Fernández-Tussy P, Wong C, Wang H, Ojima I, Kaczocha M, Perry R, Suárez Y, Fernández-Hernando C. Fatty acid binding protein 5 suppression attenuates obesity-induced hepatocellular carcinoma by promoting ferroptosis and intratumoral immune rewiring. Nature Metabolism 2024, 6: 741-763. PMID: 38664583, DOI: 10.1038/s42255-024-01019-6.Peer-Reviewed Original ResearchConceptsFatty acid binding protein 5Tumor-associated macrophagesHepatocellular carcinomaImmunosuppressive phenotype of tumor-associated macrophagesIncreased CD8+ T cell activationCD8+ T cell activationPhenotype of tumor-associated macrophagesPro-inflammatory tumor microenvironmentCo-stimulatory molecules CD80T cell activationHepatocellular carcinoma burdenTransformation of hepatocytesBinding protein 5Potential therapeutic approachImmunosuppressive phenotypeTumor microenvironmentFerroptosis-induced cell deathMale miceEnhanced ferroptosisTherapeutic approachesPharmacological inhibitionGenetic ablationIncreased expressionSingle-cell atlasAnalysis of transformed cells
2015
Th17 cells transdifferentiate into regulatory T cells during resolution of inflammation
Gagliani N, Vesely M, Iseppon A, Brockmann L, Xu H, Palm NW, de Zoete MR, Licona-Limón P, Paiva RS, Ching T, Weaver C, Zi X, Pan X, Fan R, Garmire LX, Cotton MJ, Drier Y, Bernstein B, Geginat J, Stockinger B, Esplugues E, Huber S, Flavell RA. Th17 cells transdifferentiate into regulatory T cells during resolution of inflammation. Nature 2015, 523: 221-225. PMID: 25924064, PMCID: PMC4498984, DOI: 10.1038/nature14452.Peer-Reviewed Original ResearchConceptsRegulatory T cellsResolution of inflammationInflammatory diseasesT cellsTh17 cellsImmune responseT helper cell typeTherapeutic opportunitiesAnti-inflammatory fateT helper cellsAnti-inflammatory phenotypeHuman inflammatory diseasesBeneficial host responseAryl hydrocarbon receptorIL-17ARegulatory cellsHelper cellsSignature cytokinesMouse modelTranscriptional profilesHost responseInflammationCytokinesHydrocarbon receptorDisease
2012
Effector CD4+ T Cell Expression Signatures and Immune-Mediated Disease Associated Genes
Zhang W, Ferguson J, Ng SM, Hui K, Goh G, Lin A, Esplugues E, Flavell RA, Abraham C, Zhao H, Cho JH. Effector CD4+ T Cell Expression Signatures and Immune-Mediated Disease Associated Genes. PLOS ONE 2012, 7: e38510. PMID: 22715389, PMCID: PMC3371029, DOI: 10.1371/journal.pone.0038510.Peer-Reviewed Original ResearchConceptsDifferential gene expressionGenome-wide association studiesGene expressionCell differentiationDisease locusT cell differentiationExpression signaturesDifferential regulation patternsDisease association signalsDisease-associated genesPromoter methylation studiesGenomic lociTransmembrane domainRegulation patternsFunctional pathwaysAssociation studiesMethylation studiesAssociated geneAbundant isoformGenesLociMolecular resolutionPromoter methylationRNAseqCritical roleMir-33 regulates cell proliferation and cell cycle progression
Cirera-Salinas D, Pauta M, Allen RM, Salerno AG, Ramírez CM, Chamorro-Jorganes A, Wanschel AC, Lasuncion MA, Morales-Ruiz M, Suarez Y, Baldan A, Esplugues E, Fernández-Hernando C. Mir-33 regulates cell proliferation and cell cycle progression. Cell Cycle 2012, 11: 922-933. PMID: 22333591, PMCID: PMC3323796, DOI: 10.4161/cc.11.5.19421.Peer-Reviewed Original ResearchConceptsCell cycle progressionCyclin-dependent kinase 6Cycle progressionCell proliferationCell cycle regulationMiR-33Expression of genesCyclin D1Cell cycle arrestSREBP genesCycle regulationFatty acid metabolismHost genesPosttranscriptional levelGene expressionIntronic sequencesKinase 6Cellular growthCritical regulatorCycle arrestCellular levelLiver regenerationGenesMiR-33 expressionAcid metabolism
2011
Development of Autoimmune Diabetes in the Absence of Detectable IL-17A in a CD8-Driven Virally Induced Model
Van Belle TL, Esplugues E, Liao J, Juntti T, Flavell RA, von Herrath MG. Development of Autoimmune Diabetes in the Absence of Detectable IL-17A in a CD8-Driven Virally Induced Model. The Journal Of Immunology 2011, 187: 2915-2922. PMID: 21832162, PMCID: PMC3169711, DOI: 10.4049/jimmunol.1000180.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell SeparationDiabetes Mellitus, Type 1Disease Models, AnimalFemaleFlow CytometryGene Knock-In TechniquesGenes, ReporterGreen Fluorescent ProteinsInterleukin-17Lymphocytic choriomeningitis virusMaleMiceMice, Inbred C57BLVirus DiseasesConceptsType 1 diabetesIL-17AIL-17IL-17A.T cellsViral infectionAutoimmune diabetes developmentVirus-induced modelIL-17 levelsIL-17A productionΓδ T cellsLymphocytic choriomeningitis virusAutoimmune diabetesAutoimmune disordersChronic inflammationDiabetes developmentViral eliminationReporter miceDiabetesBacterial infectionsInfectionCD8Recent studiesCellsInflammationControl of TH17 cells occurs in the small intestine
Esplugues E, Huber S, Gagliani N, Hauser AE, Town T, Wan YY, O’Connor W, Rongvaux A, Van Rooijen N, Haberman AM, Iwakura Y, Kuchroo VK, Kolls JK, Bluestone JA, Herold KC, Flavell RA. Control of TH17 cells occurs in the small intestine. Nature 2011, 475: 514-518. PMID: 21765430, PMCID: PMC3148838, DOI: 10.1038/nature10228.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodiesCD3 ComplexCD4-Positive T-LymphocytesCell MovementChemokine CCL20Disease Models, AnimalEncephalomyelitis, Autoimmune, ExperimentalFemaleGene Expression ProfilingGene Expression RegulationInfluenza A virusInterleukin-17Intestine, SmallMaleMiceMice, Inbred BALB CMice, Inbred C57BLMice, TransgenicOrthomyxoviridae InfectionsReceptors, CCR6SepsisStaphylococcal InfectionsTh17 CellsConceptsTh17 cellsImmune systemSmall intestineCD3-specific antibodiesT helper cellsModel of sepsisNumerous autoimmune diseasesRheumatoid arthritisMultiple sclerosisAutoimmune diseasesHelper cellsGastrointestinal tractViral infectionIntestineCellsSepsisTh17ArthritisSclerosisPathogenesisInfectionInfluenzaDiseaseMiceTract
2005
Induction of tumor NK-cell immunity by anti-CD69 antibody therapy
Esplugues E, Vega-Ramos J, Cartoixà D, Vazquez BN, Salaet I, Engel P, Lauzurica P. Induction of tumor NK-cell immunity by anti-CD69 antibody therapy. Blood 2005, 105: 4399-4406. PMID: 15692061, DOI: 10.1182/blood-2004-10-3854.Peer-Reviewed Original ResearchConceptsAntitumor responseNK cell cytolytic activityMonoclonal antibodiesCD69 monoclonal antibodiesNK cell immunityNK cytotoxic activityInterferon-gamma productionTGF-beta productionActivation marker CD69Production of cytokinesInnate immune systemReceptor-independent mannerNK cellsAntibody therapyLung metastasesCD69 expressionTherapeutic administrationCD69 mAbImmune responseCytolytic activityGamma productionImmune systemTumor growthTumor primingCD69
2004
Identification and characterization of a novel spliced variant that encodes human soluble tumor necrosis factor receptor 2
Lainez B, Fernandez-Real J, Romero X, Esplugues E, Cañete J, Ricart W, Engel P. Identification and characterization of a novel spliced variant that encodes human soluble tumor necrosis factor receptor 2. International Immunology 2004, 16: 169-177. PMID: 14688072, DOI: 10.1093/intimm/dxh014.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAlternative SplicingAnimalsArthritis, RheumatoidBase SequenceChlorocebus aethiopsCloning, MolecularCOS CellsEnzyme-Linked Immunosorbent AssayEtanerceptFemaleHumansImmunoglobulin GMaleMiddle AgedMolecular Sequence DataProtein IsoformsReceptors, Tumor Necrosis FactorSepsisTransfectionTumor Necrosis Factor-alphaConceptsAlternative splicingCell death inductionTNF-alpha-induced apoptosisExtracellular ectodomainMultiple inflammatory pathologiesCytoplasmic domainNovel isoformHuman TNFR2COS cellsExpression studiesDeath inductionCell typesTNF-alpha functionReceptors TNFR1SplicingExon 7Soluble formIsoformsBiological effectsBiological activityTumor necrosis factor receptor 2Pleiotropic cytokineNecrosis factor receptor 2Factor receptor 2TNFR2