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 ResearchConceptsTfh 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
2020
CD4+ follicular regulatory T cells optimize the influenza virus–specific B cell response
Lu Y, Jiang R, Freyn AW, Wang J, Strohmeier S, Lederer K, Locci M, Zhao H, Angeletti D, O’Connor K, Kleinstein SH, Nachbagauer R, Craft J. CD4+ follicular regulatory T cells optimize the influenza virus–specific B cell response. Journal Of Experimental Medicine 2020, 218: e20200547. PMID: 33326020, PMCID: PMC7748821, DOI: 10.1084/jem.20200547.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibody FormationAntigensB-LymphocytesCD4 AntigensDisease Models, AnimalEpitopesForkhead Transcription FactorsGerminal CenterHumansImmunityImmunologic MemoryInfluenza, HumanInfluenzavirus BIntegrasesMice, Inbred C57BLOrthomyxoviridae InfectionsReceptors, Antigen, B-CellSpecies SpecificityT-Lymphocytes, RegulatoryVaccinationConceptsB cell responsesGerminal center B cell responsesFollicular regulatory T cellsRegulatory T cellsTfr cellsCell responsesT cellsViral challengeHumoral memoryVirus-specific B cell responsesAntigen-specific B cell responsesFollicular helper T cellsHA stalk regionHelper T cellsInfluenza virus infectionGerminal center developmentAntibody responsePlasma cellsVirus infectionImmunization modelAntibody productionBCR repertoireInfluenza virusRepeated exposureInfluenza virus glycoproteins
2019
Spatial 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 ResearchConceptsHelper 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 development
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 survivalInterleukin-10 from CD4+ follicular regulatory T cells promotes the germinal center response
Laidlaw BJ, Lu Y, Amezquita RA, Weinstein JS, Vander Heiden JA, Gupta NT, Kleinstein SH, Kaech SM, Craft J. Interleukin-10 from CD4+ follicular regulatory T cells promotes the germinal center response. Science Immunology 2017, 2 PMID: 29054998, PMCID: PMC5846620, DOI: 10.1126/sciimmunol.aan4767.Peer-Reviewed Original ResearchConceptsFollicular regulatory T cellsRegulatory T cellsIL-10Lymphocytic choriomeningitis virusT cellsB cellsInterleukin-10GC responseCell-derived IL-10Follicular helper T cellsHelper T cellsB cell responsesGerminal center responseGerminal center developmentActivated B cellsBox protein 1GC B cellsAcute infectionCenter responseCell responsesImportant mediatorNuclear translocationGC reactionProtein 1Forkhead box protein 1
2016
AI-22 Single cell protein and transcriptional profiling of CD4+ follicular B helper T (TFH) and central memory (TCM) cells in SLE: physiological and pathological phenotypes
Kwak M, Choi J, Kim S, Chen Z, Lee G, Craft J, Fan R. AI-22 Single cell protein and transcriptional profiling of CD4+ follicular B helper T (TFH) and central memory (TCM) cells in SLE: physiological and pathological phenotypes. Lupus Science & Medicine 2016, 3: a11. DOI: 10.1136/lupus-2016-000179.22.Peer-Reviewed Original ResearchCentral memory cellsTCM cellsTfh cellsSLE patientsHealthy donorsT cellsFollicular B helper T cellsSystemic lupus erythematosusCirculation of patientsHelper T cellsSLE T cellsLupus kidneysHumoral autoimmunityTranscriptional profilingIL-21Lupus erythematosusCytokine producersHelper TMurine lupusHumoral immunityLymphoid organsEnd organsLupus researchPathological outcomesTherapeutic targetTFH 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 FactorsConceptsFollicular helper T cellsHelper T cellsGerminal center responseTfh cellsT cellsCenter responseCells
2015
The 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 balanceProgressive differentiation of follicular B helper T cells regulates the germinal center response (IRC11P.430)
Herman E, Weinstein J, Lainez B, Licona-Limón P, Esplugues E, Flavell R, Craft J. Progressive differentiation of follicular B helper T cells regulates the germinal center response (IRC11P.430). The Journal Of Immunology 2015, 194: 197.12-197.12. DOI: 10.4049/jimmunol.194.supp.197.12.Peer-Reviewed Original ResearchFollicular B helper T cellsHelper T cellsTfh cellsGerminal centersT cellsIL-21IL-4Thymus-dependent humoral immune responsesIL-21 mRNAB cell folliclesTfh cell differentiationCD4 T cellsHumoral immune responseSecondary lymphoid organsEffective antibody responseGerminal center responseAntibody-secreting cellsActivated B cellsTranscription factor Bcl6B cell maturationAntibody responseLymphoid organsImmune responseB cellsCenter response
2014
PPARγ 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 cellsAberant expansion of CXCR5+ memory CD4 T cells in SLE patients (HUM7P.307)
Choi J, Kim S, Kang I, Craft J. Aberant expansion of CXCR5+ memory CD4 T cells in SLE patients (HUM7P.307). The Journal Of Immunology 2014, 192: 184.16-184.16. DOI: 10.4049/jimmunol.192.supp.184.16.Peer-Reviewed Original ResearchCD4 T cellsSLE patientsT cellsTfh cellsB cellsB collaborationB cell helper functionFollicular helper T cellsMemory CD4 T cellsMemory Tfh cellsTh17-like subsetsAnti-nuclear antibodiesHelper T cellsB cell responsesHuman lupus patientsSecondary lymphoid organsMemory B cellsAutoreactive B cellsSuch cellsDistinct Th1Autoantibody titersDisease activityLupus patientsIL-21Lymphoid organsTranscription factor Ascl2 limits Tfh cell differentiation and function (IRC8P.493)
Bertino S, Dong X, Laidlaw B, Craft J. Transcription factor Ascl2 limits Tfh cell differentiation and function (IRC8P.493). The Journal Of Immunology 2014, 192: 190.21-190.21. DOI: 10.4049/jimmunol.192.supp.190.21.Peer-Reviewed Original ResearchTfh cellsIL-4T cellsAntibody productionCD4 T cell compartmentFollicular helper T cellsTfh cell subsetsTfh cell differentiationTfh cell developmentIL-4 productionT cell compartmentHelper T cellsLarge germinal centersGerminal center responseSecretion of cytokinesGerminal center formationB cell maturationGC B cellsIL-21Germinal centersB cellsCenter responseCell maturationConditional deletionMiceTranscription 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
2012
Follicular helper T cells in immunity and systemic autoimmunity
Craft JE. Follicular helper T cells in immunity and systemic autoimmunity. Nature Reviews Rheumatology 2012, 8: 337-347. PMID: 22549246, PMCID: PMC3604997, DOI: 10.1038/nrrheum.2012.58.Peer-Reviewed Original ResearchConceptsFollicular helper T cellsHelper T cellsT cellsSelf-reactive B cell clonesT helper cell populationSystemic lupus erythematosusSystemic autoimmune diseaseNormal immune responseT cell helpB cell clonesB cell survivalLupus erythematosusAutoantibody productionAutoimmune diseasesSystemic autoimmunityImmune responseAutoimmunityKey regulatorErythematosusCellsDiseaseImmunityT cells that promote B‐Cell maturation in systemic autoimmunity
Weinstein JS, Hernandez SG, Craft J. T cells that promote B‐Cell maturation in systemic autoimmunity. Immunological Reviews 2012, 247: 160-171. PMID: 22500839, PMCID: PMC3334351, DOI: 10.1111/j.1600-065x.2012.01122.x.Peer-Reviewed Original ResearchConceptsSystemic autoimmunityT cellsB cell maturationExtrafollicular fociGerminal centersB cellsTfh cellsImmune responseFollicular helper T cellsT cell-dependent immune responsesEnd-organ injuryB cell folliclesSystemic autoimmune diseaseTfh cell developmentHuman Tfh cellsSelf-reactive B cellsT helper cellsHelper T cellsSecondary lymphoid organsNormal immune responseT cell helpPlasma cell formationPathogenic autoantibodiesLymph nodesAutoimmune diseases
2011
Migrating out of the zone: the role of P-selectin glycoprotein ligand-1 on T follicular helper cell movement (60.8)
Hernandez S, Weinstein J, Steiner L, Bertino S, Poholek A, Gallagher P, Craft J. Migrating out of the zone: the role of P-selectin glycoprotein ligand-1 on T follicular helper cell movement (60.8). The Journal Of Immunology 2011, 186: 60.8-60.8. DOI: 10.4049/jimmunol.186.supp.60.8.Peer-Reviewed Original ResearchTfh cellsB cell folliclesT cell zonesGerminal centersT cellsLymphoid organsImmune responseB cellsFollicular helper T cellsTD immune responsesT-cell infiltratesChemokine receptor expressionHelper T cellsSecondary lymphoid organsCell zoneMemory B cellsDependent immune responsesGC B cellsWild-type controlsAdoptive transferCell infiltrateLymph nodesP-selectin glycoprotein ligand-1Plasma cell developmentDeficient miceUpregulation of Bcl6 expression in Follicular Helper T cells (TFH) requires both dendritic and antigen-specific B cell help. (63.10)
Weinstein J, Poholek A, Hernandez S, Nowyhead H, Bertino S, Craft J. Upregulation of Bcl6 expression in Follicular Helper T cells (TFH) requires both dendritic and antigen-specific B cell help. (63.10). The Journal Of Immunology 2011, 186: 63.10-63.10. DOI: 10.4049/jimmunol.186.supp.63.10.Peer-Reviewed Original ResearchTfh cell developmentCD4 T cellsAg-specific B cellsDendritic cellsT cellsB cellsFollicular entryTfh cellsBCL6 expressionTCR transgenic CD4 T cellsFollicular helper T cellsT cell surface markersTransgenic CD4 T cellsTfh cell markersTfh cell phenotypeDonor T cellsB cell helpHelper T cellsB-cell CLL/lymphoma 6Polyclonal B cellsFunctional B cellsCell developmentCell surface markersNP-OVAWild-type controlsCharacterization of different subsets of human follicular helper T (TFH) cells (152.9)
Choi J, Kim S, Lainez B, Craft J. Characterization of different subsets of human follicular helper T (TFH) cells (152.9). The Journal Of Immunology 2011, 186: 152.9-152.9. DOI: 10.4049/jimmunol.186.supp.152.9.Peer-Reviewed Original ResearchFollicular helper T cellsB cell folliclesHelper T cellsTfh cellsT cellsIL-21P-selectin glycoprotein ligand-1IL-4Germinal centersB cellsTonsillar Tfh cellsIL-17 secretionExpression of CD127B cell helpAntigen-specific antibodiesGC B cellsTh17 cellsTfh subsetsPD-1Effector subsetsCell helpTherapeutic targetBCL-6RORC expressionHuman tonsils
2010
In Vivo Regulation of Bcl6 and T Follicular Helper Cell Development
Poholek AC, Hansen K, Hernandez SG, Eto D, Chandele A, Weinstein JS, Dong X, Odegard JM, Kaech SM, Dent AL, Crotty S, Craft J. In Vivo Regulation of Bcl6 and T Follicular Helper Cell Development. The Journal Of Immunology 2010, 185: 313-326. PMID: 20519643, PMCID: PMC2891136, DOI: 10.4049/jimmunol.0904023.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell CommunicationCell DifferentiationCricetinaeDNA-Binding ProteinsDown-RegulationFemaleImmunophenotypingLymphocyte CooperationMembrane GlycoproteinsMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutMice, TransgenicProto-Oncogene Proteins c-bcl-6SpleenT-Lymphocyte SubsetsT-Lymphocytes, Helper-InducerUp-RegulationConceptsPD-1 upregulationIL-21IL-6B cellsFollicular helper T cellsFollicular helper cell developmentDeath receptor-1Helper T cellsCytokines IL-6B cell interactionsB cell maturationTranscriptional repressor BCL6Vivo regulationCell developmentP-selectin glycoprotein ligand-1New surface markersT cellsGerminal centersInitial upregulationReceptor 1CXCR5BCL6 upregulationCell maturationSurface markersBCL6 expression