2023
AP-1–independent NFAT signaling maintains follicular T cell function in infection and autoimmunity
Seth A, Yokokura Y, Choi J, Shyer J, Vidyarthi A, Craft J. AP-1–independent NFAT signaling maintains follicular T cell function in infection and autoimmunity. Journal Of Experimental Medicine 2023, 220: e20211110. PMID: 36820828, PMCID: PMC9998660, DOI: 10.1084/jem.20211110.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoimmunityB-LymphocytesCell DifferentiationGerminal CenterMiceT-Lymphocytes, Helper-InducerTranscription Factor AP-1ConceptsTfh cellsT cellsFollicular helper T cellsLupus-prone miceT cell subsetsTfh cell developmentHelper T cellsHumoral immune responseT cell functionGerminal center B cellsT cell statesRenal injuryAutoantibody productionCell subsetsPrimary T cellsImmune responseB cellsPharmacologic inhibitionTherapeutic insightsCell functionGenetic disruptionNFATCell developmentCellsGene expression
2022
High-affinity, neutralizing antibodies to SARS-CoV-2 can be made without T follicular helper cells
Chen JS, Chow RD, Song E, Mao T, Israelow B, Kamath K, Bozekowski J, Haynes WA, Filler RB, Menasche BL, Wei J, Alfajaro MM, Song W, Peng L, Carter L, Weinstein JS, Gowthaman U, Chen S, Craft J, Shon JC, Iwasaki A, Wilen CB, Eisenbarth SC. High-affinity, neutralizing antibodies to SARS-CoV-2 can be made without T follicular helper cells. Science Immunology 2022, 7: eabl5652. PMID: 34914544, PMCID: PMC8977051, DOI: 10.1126/sciimmunol.abl5652.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionSARS-CoV-2Follicular helper cellsB cell responsesHelper cellsAntibody productionCell responsesSARS-CoV-2 vaccinationB-cell receptor sequencingSevere COVID-19Cell receptor sequencingIndependent antibodiesT cell-B cell interactionsViral inflammationAntiviral antibodiesImmunoglobulin class switchingVirus infectionGerminal centersViral infectionClonal repertoireInfectionAntibodiesClass switchingCOVID-19Patients
2021
CD4+ T cells that help B cells – a proposal for uniform nomenclature
Eisenbarth SC, Baumjohann D, Craft J, Fazilleau N, Ma CS, Tangye SG, Vinuesa CG, Linterman MA. CD4+ T cells that help B cells – a proposal for uniform nomenclature. Trends In Immunology 2021, 42: 658-669. PMID: 34244056, PMCID: PMC8324560, DOI: 10.1016/j.it.2021.06.003.Peer-Reviewed Original ResearchMeSH KeywordsB-LymphocytesCell DifferentiationGerminal CenterImmunity, HumoralLymphocyte ActivationT-Lymphocytes, Helper-InducerConceptsTfh-like cellsB cellsT cellsFollicular helper cellsAntigen-primed B cellsSecondary lymphoid tissuesTranscription factor Bcl6B cell differentiationHelper cellsHumoral immunityLymphoid tissueChemokine receptorsAnatomical sitesImmune challengeDistinct subsetsDifferent isotypesCD4TfhCellular plasticityCellsCell differentiationUniform nomenclatureCytokinesImmunityAntibodies
2019
Identification of a T follicular helper cell subset that drives anaphylactic IgE
Gowthaman U, Chen JS, Zhang B, Flynn WF, Lu Y, Song W, Joseph J, Gertie JA, Xu L, Collet MA, Grassmann JDS, Simoneau T, Chiang D, Berin MC, Craft JE, Weinstein JS, Williams A, Eisenbarth SC. Identification of a T follicular helper cell subset that drives anaphylactic IgE. Science 2019, 365 PMID: 31371561, PMCID: PMC6901029, DOI: 10.1126/science.aaw6433.Peer-Reviewed Original ResearchConceptsInterleukin-4B cellsFollicular Helper Cell SubsetsLow-affinity IgEFollicular helper cellsAllergen-specific IgEHelper cell subsetsIsotypes of antibodiesAlternative therapeutic targetsTranscription factor Bcl6Anaphylactic IgECytokine profileIgE productionCell subsetsHelper cellsImmunoglobulin ETherapeutic targetIgEAnaphylaxisAllergensCellular mechanismsRare populationCellsMiceGATA3Spatial and functional heterogeneity of follicular helper T cells in autoimmunity
Seth A, Craft J. Spatial and functional heterogeneity of follicular helper T cells in autoimmunity. Current Opinion In Immunology 2019, 61: 1-9. PMID: 31374450, PMCID: PMC7255639, DOI: 10.1016/j.coi.2019.06.005.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoantibodiesAutoimmune DiseasesAutoimmunityBiomarkersB-LymphocytesCytokinesGerminal CenterHumansMolecular Targeted TherapyT-Lymphocytes, Helper-InducerConceptsHelper T cellsFollicular helper T cellsT cellsB cell helper T cellsTfh cell biologyB cell folliclesB cell helpT helper cellsNon-lymphoid tissuesAutoantibody-mediated autoimmunitySecondary lymphoidAutoimmune diseasesHelper cellsCell helpGerminal centersAnimal modelsB cell developmentHuman patientsPathogenic changesAutoimmunityProduction of affinityExtrafollicular spaceTherapeutic purposesFunctional heterogeneityCell developmentT follicular helper cell heterogeneity: Time, space, and function
Song W, Craft J. T follicular helper cell heterogeneity: Time, space, and function. Immunological Reviews 2019, 288: 85-96. PMID: 30874350, PMCID: PMC6422039, DOI: 10.1111/imr.12740.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibody AffinityB-LymphocytesCell DifferentiationCell PlasticityGerminal CenterHumansImmunity, HumoralImmunologic MemoryPlasma CellsT-Lymphocyte SubsetsT-Lymphocytes, Helper-Inducer
2018
Human Extrafollicular CD4+ Th Cells Help Memory B Cells Produce Igs.
Kim ST, Choi JY, Lainez B, Schulz VP, Karas DE, Baum ED, Setlur J, Gallagher PG, Craft J. Human Extrafollicular CD4+ Th Cells Help Memory B Cells Produce Igs. The Journal Of Immunology 2018, 201: 1359-1372. PMID: 30030323, PMCID: PMC6112860, DOI: 10.4049/jimmunol.1701217.Peer-Reviewed Original ResearchConceptsMemory B cellsHumoral recall responsesB cell folliclesT cell subsetsB cellsTfh cellsCell subsetsRecall responsesT cellsInhibitory receptor PD-1Follicular helper T cellsGerminal center B-cell maturationIL-21 secretionChemokine receptor expressionReceptor PD-1Helper T cellsT cell zonesPrimary immune responseChemokine receptor CXCR5Transcription factor Bcl6B cell maturationTonsillar CD4IL-10IL-21PD-1
2017
STAT4 and T-bet control follicular helper T cell development in viral infections
Weinstein JS, Laidlaw BJ, Lu Y, Wang JK, Schulz VP, Li N, Herman EI, Kaech SM, Gallagher PG, Craft J. STAT4 and T-bet control follicular helper T cell development in viral infections. Journal Of Experimental Medicine 2017, 215: 337-355. PMID: 29212666, PMCID: PMC5748849, DOI: 10.1084/jem.20170457.Peer-Reviewed Original ResearchConceptsIL-21Tfh cellsT-betViral infectionFollicular helper T cellsHelper T cell developmentAcute viral infectionIFN-γ productionHelper T cellsGerminal center B cell survivalB cell survivalT cell developmentIL-4Viral challengeIL-9T cellsImmunoglobulin isotypesIFNSoluble factorsGC responseInfectionGC reactionSTAT4BCL6Cell survivalDisruption of Pathogenic Cellular Networks by IL-21 Blockade Leads to Disease Amelioration in Murine Lupus.
Choi JY, Seth A, Kashgarian M, Terrillon S, Fung E, Huang L, Wang LC, Craft J. Disruption of Pathogenic Cellular Networks by IL-21 Blockade Leads to Disease Amelioration in Murine Lupus. The Journal Of Immunology 2017, 198: 2578-2588. PMID: 28219887, PMCID: PMC5360548, DOI: 10.4049/jimmunol.1601687.Peer-Reviewed Original ResearchConceptsIL-21Systemic lupus erythematosusMurine lupusTfh cellsLupus erythematosusDisease ameliorationGerminal center B cell responsesTfh-B cell interactionsGC responseFollicular Th cellsIL-21 blockadeLupus-prone B6Progression of glomerulonephritisCell-derived cytokinesB cell responsesMemory B cell developmentPotential therapeutic strategyB cell proliferationB cell maturationGC B cellsOverall survivalOrgan injuryAutoantibody productionLatter cytokineTh cells
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 Factors
2015
Reply
Choi J, Craft J. Reply. Arthritis & Rheumatology 2015, 67: 3094-3095. PMID: 26245163, DOI: 10.1002/art.39290.Peer-Reviewed Original ResearchCD4-Positive T-LymphocytesFemaleHumansLupus Erythematosus, SystemicMaleT-Lymphocytes, Helper-InducerThe Interleukin-2-mTORc1 Kinase Axis Defines the Signaling, Differentiation, and Metabolism of T Helper 1 and Follicular B Helper T Cells
Ray JP, Staron MM, Shyer JA, Ho PC, Marshall HD, Gray SM, Laidlaw BJ, Araki K, Ahmed R, Kaech SM, Craft J. The Interleukin-2-mTORc1 Kinase Axis Defines the Signaling, Differentiation, and Metabolism of T Helper 1 and Follicular B Helper T Cells. Immunity 2015, 43: 690-702. PMID: 26410627, PMCID: PMC4618086, DOI: 10.1016/j.immuni.2015.08.017.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCalcium SignalingCell CycleCell DivisionEnzyme ActivationGlucoseGlycolysisInterleukin-2Interleukin-2 Receptor alpha SubunitLymphocytic choriomeningitis virusMechanistic Target of Rapamycin Complex 1Mice, Inbred C57BLMultiprotein ComplexesNFATC Transcription FactorsOxygen ConsumptionPositive Regulatory Domain I-Binding Factor 1Proto-Oncogene Proteins c-aktSignal TransductionSpecific Pathogen-Free OrganismsTh1 CellsT-Lymphocyte SubsetsT-Lymphocytes, Helper-InducerTOR Serine-Threonine KinasesTranscription FactorsConceptsFollicular B helper T cellsAcute viral infectionHelper T cellsTfh cellsT cellsViral infectionT helper 1 cellsHelper T cell subsetsIL-2-mediated activationT cell subsetsDiverse effector functionsT helper 1Dependent cytokine productionTh1 cell fateHelper 1Cell subsetsCytokine productionTh1 cellsInterleukin-2Effector functionsCritical orchestratorsMTOR kinase activityLess proliferationMTORC1 axisReciprocal balanceCirculating Follicular Helper–Like T Cells in Systemic Lupus Erythematosus: Association With Disease Activity
Choi J, Ho J, Pasoto SG, Bunin V, Kim ST, Carrasco S, Borba EF, Gonçalves CR, Costa PR, Kallas EG, Bonfa E, Craft J. Circulating Follicular Helper–Like T Cells in Systemic Lupus Erythematosus: Association With Disease Activity. Arthritis & Rheumatology 2015, 67: 988-999. PMID: 25581113, PMCID: PMC4450082, DOI: 10.1002/art.39020.Peer-Reviewed Original ResearchMeSH KeywordsAdultAutoantibodiesBehcet SyndromeCD4-Positive T-LymphocytesDNAFemaleHumansInterleukinsLupus Erythematosus, SystemicMaleMiddle AgedSeverity of Illness IndexT-Lymphocytes, Helper-InducerConceptsTfh-like cellsSLE Disease Activity IndexSystemic lupus erythematosusInducible T-cell costimulatorPD-1 expressionDisease activityT cellsBehçet's diseaseSLE patientsLupus erythematosusBlood samplesT cell-B cell collaborationCentral memory T cellsExpression of CXCR5Disease activity indexGerminal center activityMemory T cellsDeath 1 proteinFollicular helper TT-cell costimulatorActive diseaseAntibody positivityDisease durationFollicular helperIL-21Local Triggering of the ICOS Coreceptor by CD11c+ Myeloid Cells Drives Organ Inflammation in Lupus
Teichmann LL, Cullen JL, Kashgarian M, Dong C, Craft J, Shlomchik MJ. Local Triggering of the ICOS Coreceptor by CD11c+ Myeloid Cells Drives Organ Inflammation in Lupus. Immunity 2015, 42: 552-565. PMID: 25786178, PMCID: PMC4456685, DOI: 10.1016/j.immuni.2015.02.015.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisAutoantibodiesCD11c AntigenCell DifferentiationFemaleGene Expression RegulationHumansInducible T-Cell Co-Stimulator LigandInducible T-Cell Co-Stimulator ProteinKidneyLungLupus NephritisMice, TransgenicPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktSignal TransductionT-Lymphocytes, Helper-InducerConceptsInducible T-cell costimulatorOrgan inflammationICOS ligandFollicular helper cell differentiationLupus-prone MRLT-cell costimulatorHelper cell differentiationLupus pathologyLung inflammationAutoantibody formationAutoantibody productionMurine lupusInflamed organsLymphoid tissueT cellsB cellsPathogenic relevanceInflammationLupusPI3K-AktSelective ablationCell differentiationNonredundant rolePotent promoterCellsThe transforming growth factor beta signaling pathway is critical for the formation of CD4 T follicular helper cells and isotype-switched antibody responses in the lung mucosa
Marshall HD, Ray JP, Laidlaw BJ, Zhang N, Gawande D, Staron MM, Craft J, Kaech SM. The transforming growth factor beta signaling pathway is critical for the formation of CD4 T follicular helper cells and isotype-switched antibody responses in the lung mucosa. ELife 2015, 4: e04851. PMID: 25569154, PMCID: PMC4337607, DOI: 10.7554/elife.04851.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibody FormationB-LymphocytesCell DifferentiationGene Expression ProfilingGerminal CenterImmunoglobulin Class SwitchingLungMiceMucous MembraneOrthomyxoviridaeOrthomyxoviridae InfectionsSignal TransductionSpecies SpecificityT-Lymphocytes, Helper-InducerTOR Serine-Threonine KinasesTransforming Growth Factor betaConceptsCD4 T cellsFollicular helper cellsTfh cellsAntibody responseT cellsHelper cellsViral infectionCD4 T follicular helper cellsVirus-specific CD4 T cellsIL-2 receptor α chainT Follicular Helper CellsRespiratory viral infectionsAcute viral infectionGrowth factor betaGerminal center reactionReceptor α chainInhibition of mTORIL-2 signalingLung mucosaTfh differentiationHumoral responseRapamycin (mTOR) activationTGF-βRFactor betaCenter reaction
2014
Global transcriptome analysis and enhancer landscape of human primary T follicular helper and T effector lymphocytes
Weinstein JS, Lezon-Geyda K, Maksimova Y, Craft S, Zhang Y, Su M, Schulz VP, Craft J, Gallagher PG. Global transcriptome analysis and enhancer landscape of human primary T follicular helper and T effector lymphocytes. Blood 2014, 124: 3719-3729. PMID: 25331115, PMCID: PMC4263981, DOI: 10.1182/blood-2014-06-582700.Peer-Reviewed Original ResearchConceptsT-cell lymphomaTfh cellsHelper cellsPrimary cutaneous T-cell lymphomaAngioimmunoblastic T-cell lymphomaCutaneous T-cell lymphomaTfh cell functionFollicular helper cellsT effector cellsCell functionHuman Tfh cellsProtective humoral immunityT helper cellsLymphoid cell functionB cell maturationT lymphocyte developmentEffector cellsFollicular helperT effectorsAutoimmune diseasesHumoral immunityAntibody formationPlasma cellsGerminal centersLymphoid cellsDynamic signaling by T follicular helper cells during germinal center B cell selection
Shulman Z, Gitlin AD, Weinstein JS, Lainez B, Esplugues E, Flavell RA, Craft JE, Nussenzweig MC. Dynamic signaling by T follicular helper cells during germinal center B cell selection. Science 2014, 345: 1058-1062. PMID: 25170154, PMCID: PMC4519234, DOI: 10.1126/science.1257861.Peer-Reviewed Original ResearchConceptsFollicular helper cellsB cellsGC B cellsHelper cellsGerminal centersAntibody-producing B cellsCytokine interleukin-4B cell selectionGerminal center B cell selectionInterleukin-4Transient elevationMajor histocompatibilitySustained increaseFree calciumClonal expansionCognate peptideIntravital imagingCell migrationCellsIntracellularCell selectionHigh levelsHistocompatibilityPPARγ Negatively Regulates T Cell Activation to Prevent Follicular Helper T Cells and Germinal Center Formation
Park HJ, Kim DH, Choi JY, Kim WJ, Kim JY, Senejani AG, Hwang SS, Kim LK, Tobiasova Z, Lee GR, Craft J, Bothwell AL, Choi JM. PPARγ Negatively Regulates T Cell Activation to Prevent Follicular Helper T Cells and Germinal Center Formation. PLOS ONE 2014, 9: e99127. PMID: 24921943, PMCID: PMC4055678, DOI: 10.1371/journal.pone.0099127.Peer-Reviewed Original ResearchConceptsFollicular helper T cellsHelper T cellsT cellsGerminal center reactionTfh cellsSheep red blood cell immunizationRed blood cell immunizationCenter reactionPeroxisome proliferator-activated receptor gammaIL-21 expressionProliferator-activated receptor gammaWild-type T cellsType T cellsGerminal center formationGerminal center B cellsT cell activationCell immunizationAutoantibody productionGlomerular inflammationSignature cytokinesAdaptive immunityGerminal centersGlucose metabolismNF-κBB cellsB Cells in T Follicular Helper Cell Development and Function: Separable Roles in Delivery of ICOS Ligand and Antigen
Weinstein JS, Bertino SA, Hernandez SG, Poholek AC, Teplitzky TB, Nowyhed HN, Craft J. B Cells in T Follicular Helper Cell Development and Function: Separable Roles in Delivery of ICOS Ligand and Antigen. The Journal Of Immunology 2014, 192: 3166-3179. PMID: 24610013, PMCID: PMC3991608, DOI: 10.4049/jimmunol.1302617.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigensAntigens, CD19B-LymphocytesCell ProliferationDNA-Binding ProteinsFlow CytometryInducible T-Cell Co-Stimulator LigandMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicMicroscopy, ConfocalNitrophenolsOvalbuminPhenylacetatesProto-Oncogene Proteins c-bcl-6Reverse Transcriptase Polymerase Chain ReactionT-LymphocytesT-Lymphocytes, Helper-InducerConceptsCognate B cellsTfh cell developmentB cellsICOS ligandFollicular Th cell developmentCell developmentNoncognate B cellsFollicular helper cell developmentTfh cell differentiationAg-specific B cellsICOS-L expressionB cell expressionTh cell developmentGerminal center differentiationICOS blockadeTfh cellsAg deliverySystemic autoimmunityCell expressionCell maturationICOSCellsDeliveryCell differentiationCells displayTranscription Factor STAT3 and Type I Interferons Are Corepressive Insulators for Differentiation of Follicular Helper and T Helper 1 Cells
Ray JP, Marshall HD, Laidlaw BJ, Staron MM, Kaech SM, Craft J. Transcription Factor STAT3 and Type I Interferons Are Corepressive Insulators for Differentiation of Follicular Helper and T Helper 1 Cells. Immunity 2014, 40: 367-377. PMID: 24631156, PMCID: PMC3992517, DOI: 10.1016/j.immuni.2014.02.005.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, ViralAntibody SpecificityB-LymphocytesCD4 AntigensCD4-Positive T-LymphocytesCell DifferentiationGene Expression ProfilingGene Expression RegulationGerminal CenterImmunoglobulin Class SwitchingInterferon Type ILymphocytic ChoriomeningitisLymphocytic choriomeningitis virusMiceMice, KnockoutSignal TransductionSTAT1 Transcription FactorSTAT3 Transcription FactorT-Lymphocytes, Helper-InducerTranscriptomeConceptsTfh cellsType I interferonI interferonViral infectionFollicular helper T cellsT helper 1 cellsAntigen-specific antibody productionGC B cell phenotypeHigh affinity antibody-secreting cellsTfh cell differentiationHelper T cellsB cell memoryLymphocytic choriomeningitis virusB-cell phenotypeAntibody-secreting cellsGerminal center B cellsEffector phenotypeReceptor blockadeAcute infectionFollicular helperIFN-inducible genesT cellsTranscription factor STAT3B cellsAntibody production