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
2020
The induction and function of the anti-inflammatory fate of TH17 cells
Xu H, Agalioti T, Zhao J, Steglich B, Wahib R, Vesely MCA, Bielecki P, Bailis W, Jackson R, Perez D, Izbicki J, Licona-Limón P, Kaartinen V, Geginat J, Esplugues E, Tolosa E, Huber S, Flavell RA, Gagliani N. The induction and function of the anti-inflammatory fate of TH17 cells. Nature Communications 2020, 11: 3334. PMID: 32620760, PMCID: PMC7335205, DOI: 10.1038/s41467-020-17097-5.Peer-Reviewed Original Research
2018
Microbiota-driven interleukin-17-producing cells and eosinophils synergize to accelerate multiple myeloma progression
Calcinotto A, Brevi A, Chesi M, Ferrarese R, Garcia Perez L, Grioni M, Kumar S, Garbitt VM, Sharik ME, Henderson KJ, Tonon G, Tomura M, Miwa Y, Esplugues E, Flavell RA, Huber S, Canducci F, Rajkumar VS, Bergsagel PL, Bellone M. Microbiota-driven interleukin-17-producing cells and eosinophils synergize to accelerate multiple myeloma progression. Nature Communications 2018, 9: 4832. PMID: 30510245, PMCID: PMC6277390, DOI: 10.1038/s41467-018-07305-8.Peer-Reviewed Original ResearchConceptsIL-17Multiple myelomaTh17 cellsDisease progressionBone marrowInterleukin-17-producing cellsFaster disease progressionMultiple myeloma progressionExtramucosal tumorsMM patientsAvailable therapiesIL-17RAIL-5Myeloma progressionPlasma cellsGut microbiotaCommensal bacteriaInnate immunityIntestinal microbesMurine plasma cellsPrevotella heparinolyticaEosinophilsMiceProgressionSTAT3 phosphorylation
2016
TFH cells progressively differentiate to regulate the germinal center response
Weinstein JS, Herman EI, Lainez B, Licona-Limón P, Esplugues E, Flavell R, Craft J. TFH cells progressively differentiate to regulate the germinal center response. Nature Immunology 2016, 17: 1197-1205. PMID: 27573866, PMCID: PMC5030190, DOI: 10.1038/ni.3554.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibody AffinityB-LymphocytesCD4 AntigensCell CommunicationCell DifferentiationCells, CulturedGene Expression RegulationGerminal CenterHumansInterleukin-4InterleukinsMiceMice, Inbred C57BLMice, Mutant StrainsMutationNippostrongylusPositive Regulatory Domain I-Binding Factor 1Strongylida InfectionsT-Lymphocytes, Helper-InducerTranscription FactorsApoptosis in response to microbial infection induces autoreactive TH17 cells
Campisi L, Barbet G, Ding Y, Esplugues E, Flavell RA, Blander JM. Apoptosis in response to microbial infection induces autoreactive TH17 cells. Nature Immunology 2016, 17: 1084-1092. PMID: 27455420, PMCID: PMC5079524, DOI: 10.1038/ni.3512.Peer-Reviewed Original Research
2014
The Role of TH17‐Associated Cytokines in Health and Disease
O’Connor W, Esplugues E, Huber S. The Role of TH17‐Associated Cytokines in Health and Disease. Journal Of Immunology Research 2014, 2014: 936270. PMID: 24872959, PMCID: PMC4020370, DOI: 10.1155/2014/936270.Peer-Reviewed Original Research
2012
Enhanced Anti-Serpin Antibody Activity Inhibits Autoimmune Inflammation in Type 1 Diabetes
Czyzyk J, Henegariu O, Preston-Hurlburt P, Baldzizhar R, Fedorchuk C, Esplugues E, Bottomly K, Gorus FK, Herold K, Flavell RA. Enhanced Anti-Serpin Antibody Activity Inhibits Autoimmune Inflammation in Type 1 Diabetes. The Journal Of Immunology 2012, 188: 6319-6327. PMID: 22593614, PMCID: PMC3370061, DOI: 10.4049/jimmunol.1200467.Peer-Reviewed Original ResearchConceptsAutoimmune diabetes-prone NOD miceDiabetes-prone NOD miceHuman type 1 diabetesAnti-insulin autoantibodiesOnset of diabetesProtective humoral immunityType 1 diabetesNOD miceAutoimmune inflammationIslet inflammationNOD modelSuboptimal doseAutoimmune diseasesHumoral immunityImmunological toleranceT cellsHumoral activityType 1Early onsetDiabetesElevated levelsClade B serpinsAutoantibodiesInflammationProtease inhibitorsEffector 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
miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling
Dávalos A, Goedeke L, Smibert P, Ramírez CM, Warrier NP, Andreo U, Cirera-Salinas D, Rayner K, Suresh U, Pastor-Pareja JC, Esplugues E, Fisher EA, Penalva LO, Moore KJ, Suárez Y, Lai EC, Fernández-Hernando C. miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 9232-9237. PMID: 21576456, PMCID: PMC3107310, DOI: 10.1073/pnas.1102281108.Peer-Reviewed Original ResearchConceptsFatty acid metabolismFatty acid oxidationMiR-33aInsulin receptor substrate 2Sirtuin 6Acid metabolismInsulin-signaling pathwayIntronic microRNAsSterol regulatory element-binding protein 2Acid oxidationHost genesKey enzymeHepatic cell linesMetabolic syndromeCarnitine palmitoyltransferase 1AMetabolic pathwaysSubstrate 2Cellular imbalanceProtein 2Cholesterol homeostasisGenesCell linesLevels of HDLPathwayMetabolism results
2005
The Adaptor Protein 3BP2 Binds Human CD244 and Links this Receptor to Vav Signaling, ERK Activation, and NK Cell Killing
Saborit-Villarroya I, Del Valle J, Romero X, Esplugues E, Lauzurica P, Engel P, Martín M. The Adaptor Protein 3BP2 Binds Human CD244 and Links this Receptor to Vav Signaling, ERK Activation, and NK Cell Killing. The Journal Of Immunology 2005, 175: 4226-4235. PMID: 16177062, DOI: 10.4049/jimmunol.175.7.4226.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsAntigens, CDCell Line, TumorCoculture TechniquesCytotoxicity, ImmunologicExtracellular Signal-Regulated MAP KinasesHumansInterferon-gammaKiller Cells, NaturalLigandsMembrane GlycoproteinsMicePhosphorylationReceptors, ImmunologicSignal TransductionSignaling Lymphocytic Activation Molecule FamilyYeastsConceptsERK activationSrc homology 2 domainThree-hybrid analysisDisease gene productCell surface proteinsLymphocytic activation molecule-associated proteinSAP recruitmentAdaptor proteinConsensus motifGene productsAdaptor 3BP2CD150 familySurface proteinsSAP associationPhysical interactionProteinCellular activationPhosphorylationCell killingMyeloid cellsMotifCellsActivationBindingPresent evidence
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
2003
CD69 downregulates autoimmune reactivity through active transforming growth factor-β production in collagen-induced arthritis
Sancho D, Gómez M, Viedma F, Esplugues E, Gordón-Alonso M, García-López MA, de la Fuente H, Martínez-A C, Lauzurica P, Sánchez-Madrid F. CD69 downregulates autoimmune reactivity through active transforming growth factor-β production in collagen-induced arthritis. Journal Of Clinical Investigation 2003, 112: 872-882. PMID: 12975472, PMCID: PMC193672, DOI: 10.1172/jci19112.Peer-Reviewed Original ResearchConceptsCollagen-induced arthritisCD69-/- miceAutoimmune reactivitySeverity of CIAProinflammatory cytokine mRNA levelsB cell immune responsesProinflammatory cytokines IL-1betaCD69-deficient miceRole of CD69Cell immune responsesCytokine mRNA levelsCytokines IL-1betaActivation of leukocytesTGF-beta1 productionNegative cell linesSplenocyte subsetsProinflammatory mediatorsBeta antibodyIL-1betaInflammatory fociLocal injectionSynovial leukocytesImmune responseCIA severityInflammatory sites
2001
CD84 Functions as a Homophilic Adhesion Molecule and Enhances IFN-γ Secretion: Adhesion Is Mediated by Ig-Like Domain 1
Martin M, Romero X, de la Fuente M, Tovar V, Zapater N, Esplugues E, Pizcueta P, Bosch J, Engel P. CD84 Functions as a Homophilic Adhesion Molecule and Enhances IFN-γ Secretion: Adhesion Is Mediated by Ig-Like Domain 1. The Journal Of Immunology 2001, 167: 3668-3676. PMID: 11564780, DOI: 10.4049/jimmunol.167.7.3668.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalAntigens, CDBinding, CompetitiveCell AdhesionCell Adhesion MoleculesCells, CulturedChildChild, PreschoolCOS CellsHumansImmunoglobulinsInterferon-gammaLymphocyte ActivationMembrane GlycoproteinsMiceProtein Structure, TertiarySignaling Lymphocytic Activation Molecule FamilyThymus GlandT-LymphocytesTumor Cells, CulturedConceptsFusion proteinExtracellular domainSoluble Ig fusion proteinDomain 1Homophilic adhesion moleculeFirst extracellular domainLymphoproliferative disease geneReceptor-ligand interactionsIg-like domains 1Cytoplasmic tailProtein 1ADisease genesCell surface moleculesHuman CD84Ligand-receptor recognitionCD2 familyMature T cellsCD84Own ligandConcurrent ligationMouse chimerasReceptor recognitionIg fusion proteinProteinCell maturation