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
2019
Effector TH17 Cells Give Rise to Long-Lived TRM Cells that Are Essential for an Immediate Response against Bacterial Infection
Vesely M, Pallis P, Bielecki P, Low JS, Zhao J, Harman CCD, Kroehling L, Jackson R, Bailis W, Licona-Limón P, Xu H, Iijima N, Pillai PS, Kaplan DH, Weaver CT, Kluger Y, Kowalczyk MS, Iwasaki A, Pereira JP, Esplugues E, Gagliani N, Flavell RA. Effector TH17 Cells Give Rise to Long-Lived TRM Cells that Are Essential for an Immediate Response against Bacterial Infection. Cell 2019, 178: 1176-1188.e15. PMID: 31442406, PMCID: PMC7057720, DOI: 10.1016/j.cell.2019.07.032.Peer-Reviewed Original ResearchConceptsCD4 TTissue-resident memory T cellsBacterial infectionsResident memory T cellsFunction of airwayLife-long protectionEffector memory TMemory T cellsTh17 cellsTRM cellsΓδ TEffector cellsMemory TBacterial clearanceT cellsIL-7Adaptive immunityMouse modelMemory responsesVaccine designHost defenseLymphatic endothelial cellsDepletion studiesEndothelial cellsCellular origin
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
2017
TH17 cells express ST2 and are controlled by the alarmin IL-33 in the small intestine
Pascual-Reguant A, Bayat Sarmadi J, Baumann C, Noster R, Cirera-Salinas D, Curato C, Pelczar P, Huber S, Zielinski CE, Löhning M, Hauser AE, Esplugues E. TH17 cells express ST2 and are controlled by the alarmin IL-33 in the small intestine. Mucosal Immunology 2017, 10: 1431-1442. PMID: 28198366, DOI: 10.1038/mi.2017.5.Peer-Reviewed Original ResearchConceptsPro-inflammatory TH17 cellsIntestinal epithelial cellsTh17 cellsSmall intestineIL-33IL-33/ST2 axisPro-inflammatory T cellsAlarmin IL-33Alarmin interleukin-33IL-33 receptorPro-inflammatory cytokinesAbsence of ST2Beneficial host responseIL-10Interleukin-33Autoimmune diseasesTissue inflammationInflammatory responseImmunosuppressive propertiesT cellsImmune responseInflamed tissuesHost responseImmune systemRegulatory phenotypeIL-10 Receptor Signaling Is Essential for TR1 Cell Function In Vivo
Brockmann L, Gagliani N, Steglich B, Giannou AD, Kempski J, Pelczar P, Geffken M, Mfarrej B, Huber F, Herkel J, Wan YY, Esplugues E, Battaglia M, Krebs CF, Flavell RA, Huber S. IL-10 Receptor Signaling Is Essential for TR1 Cell Function In Vivo. The Journal Of Immunology 2017, 198: 1130-1141. PMID: 28003377, PMCID: PMC5263184, DOI: 10.4049/jimmunol.1601045.Peer-Reviewed Original ResearchConceptsIL-10 receptor signalingCell regulatory activityIL-10Receptor signalingIL-10 receptor expressionRegulatory type 1 (Tr1) cellsInflammatory bowel disease modelCell therapyInflammatory bowel diseaseIL-10 productionIL-10 receptorMurine inflammatory bowel disease modelT-cell therapyType 1 cellsBowel diseaseCell-based therapiesIL-10RαClinical trialsReceptor expressionIntestinal homeostasisSuppressive activityReporter miceTransgenic miceTherapyRegulatory activity
2016
Apoptosis 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
2015
Gatekeeper role of brain antigen‐presenting CD11c+ cells in neuroinflammation
Paterka M, Siffrin V, Voss JO, Werr J, Hoppmann N, Gollan R, Belikan P, Bruttger J, Birkenstock J, Jung S, Esplugues E, Yogev N, Flavell RA, Bopp T, Zipp F. Gatekeeper role of brain antigen‐presenting CD11c+ cells in neuroinflammation. The EMBO Journal 2015, 35: 89-101. PMID: 26612827, PMCID: PMC4718005, DOI: 10.15252/embj.201591488.Peer-Reviewed Original ResearchConceptsPathogenic T cellsT cellsFrequent chronic inflammatory diseaseChronic inflammatory diseaseAntigen-presenting cellsInflammatory chemokines CCL5Autoimmune neuroinflammationPerivascular clustersTh17 cellsDendritic cellsMultiple sclerosisInflammatory diseasesChemokine CCL5Disease severityCNSGM-CSFExpression correlatesTwo-photon microscopyNeuroinflammationGatekeeper functionSurvivalCellsGatekeeper rolePotent typeImpaired enrichmentTh17 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
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 ResearchOct-1 Regulates IL-17 Expression by Directing Interchromosomal Associations in Conjunction with CTCF in T Cells
Kim LK, Esplugues E, Zorca CE, Parisi F, Kluger Y, Kim TH, Galjart NJ, Flavell RA. Oct-1 Regulates IL-17 Expression by Directing Interchromosomal Associations in Conjunction with CTCF in T Cells. Molecular Cell 2014, 54: 56-66. PMID: 24613343, PMCID: PMC4058095, DOI: 10.1016/j.molcel.2014.02.004.Peer-Reviewed Original ResearchAnimalsBinding SitesCCCTC-Binding FactorCell DifferentiationCell LineageCells, CulturedChromosomes, MammalianDeoxyribonuclease IGene Expression RegulationGenes, ReporterGenetic LociGreen Fluorescent ProteinsInterleukin-17MiceMice, Inbred C57BLMice, KnockoutMice, TransgenicOctamer Transcription Factor-1Promoter Regions, GeneticRepressor ProteinsSequence DeletionTh17 CellsTh2 CellsTime Factors
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 role
2011
Control 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 infectionIntestineCellsSepsisTh17ArthritisSclerosisPathogenesisInfectionInfluenzaDiseaseMiceTractTh17 Cells Express Interleukin-10 Receptor and Are Controlled by Foxp3− and Foxp3+ Regulatory CD4+ T Cells in an Interleukin-10-Dependent Manner
Huber S, Gagliani N, Esplugues E, O'Connor W, Huber FJ, Chaudhry A, Kamanaka M, Kobayashi Y, Booth CJ, Rudensky AY, Roncarolo MG, Battaglia M, Flavell RA. Th17 Cells Express Interleukin-10 Receptor and Are Controlled by Foxp3− and Foxp3+ Regulatory CD4+ T Cells in an Interleukin-10-Dependent Manner. Immunity 2011, 34: 554-565. PMID: 21511184, PMCID: PMC3113617, DOI: 10.1016/j.immuni.2011.01.020.Peer-Reviewed Original ResearchConceptsIL-10 signalingT cellsIL-10-dependent mannerIL-10-producing cellsIL-17A-producing CD4T cell-specific blockadeT helper 17 (Th17) cellsHelper 17 cellsIL-10 treatmentChronic inflammatory diseaseInterleukin-10 receptorRegulatory CD4Intestinal inflammationRegulatory cellsInflammatory diseasesExtracellular microorganismsReceptor αCell frequencySmall intestineHost defenseCD4Selective increaseDirect signalingVivoCells