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
2022
Tfh-cell-derived interleukin 21 sustains effector CD8+ T cell responses during chronic viral infection
Zander R, Kasmani MY, Chen Y, Topchyan P, Shen J, Zheng S, Burns R, Ingram J, Cui C, Joshi N, Craft J, Zajac A, Cui W. Tfh-cell-derived interleukin 21 sustains effector CD8+ T cell responses during chronic viral infection. Immunity 2022, 55: 475-493.e5. PMID: 35216666, PMCID: PMC8916994, DOI: 10.1016/j.immuni.2022.01.018.Peer-Reviewed Original ResearchConceptsChronic viral infectionsIL-21Cell responsesViral infectionMixed bone marrow chimera experimentsBone marrow chimera experimentsMemory-like subsetTfh cell responsesCell-mediated immunityTfh cellsEffector CD8LCMV infectionHelper subsetsInterleukin-21Th1 cellsViral controlCD8Chimera experimentsCD4InfectionCell differentiationCellsSubsetResponseDistinct populations
2021
Neoantigen-driven B cell and CD4 T follicular helper cell collaboration promotes anti-tumor CD8 T cell responses
Cui C, Wang J, Fagerberg E, Chen PM, Connolly KA, Damo M, Cheung JF, Mao T, Askari AS, Chen S, Fitzgerald B, Foster GG, Eisenbarth SC, Zhao H, Craft J, Joshi NS. Neoantigen-driven B cell and CD4 T follicular helper cell collaboration promotes anti-tumor CD8 T cell responses. Cell 2021, 184: 6101-6118.e13. PMID: 34852236, PMCID: PMC8671355, DOI: 10.1016/j.cell.2021.11.007.Peer-Reviewed Original ResearchConceptsCD8 TB cellsTfh cellsLung adenocarcinomaTfh-B cell interactionsTumor-specific B cellsFollicular helper cellsAnti-tumor immunityB cell signaturesCell effector functionsGerminal center formationGC B cellsCD4 THelper cellsTumor controlTumor neoantigensEffector functionsCell collaborationCell responsesCell signatureTumor cellsSignature correlatesNeoantigensCell functionCD4Neoantigen driven B cell and CD4+ T follicular helper cell collaboration promotes robust anti-tumor CD8+ T cell responses
Cui C, Joshi N, Craft J. Neoantigen driven B cell and CD4+ T follicular helper cell collaboration promotes robust anti-tumor CD8+ T cell responses. The Journal Of Immunology 2021, 206: 57.01-57.01. DOI: 10.4049/jimmunol.206.supp.57.01.Peer-Reviewed Original ResearchT cell responsesAnti-tumor CD8Tfh cellsB cellsCell responsesIL-21Cell collaborationProtective anti-tumor responsesTfh-B cell interactionsTumor-specific B cellsGC B cell responsesTumor-specific CD4Anti-tumor immunityFavorable clinical outcomeAnti-tumor responseIL-21 receptorB cell responsesLung adenocarcinoma patientsAnalysis of survivalT cell-B cell interactionsGerminal center formationCell interactionsGC B cellsAbstract CD4Effector CD8Type I Interferon–Activated STAT4 Regulation of Follicular Helper T Cell–Dependent Cytokine and Immunoglobulin Production in Lupus
Dong X, Antao OQ, Song W, Sanchez GM, Zembrzuski K, Koumpouras F, Lemenze A, Craft J, Weinstein JS. Type I Interferon–Activated STAT4 Regulation of Follicular Helper T Cell–Dependent Cytokine and Immunoglobulin Production in Lupus. Arthritis & Rheumatology 2021, 73: 478-489. PMID: 33512094, PMCID: PMC7914134, DOI: 10.1002/art.41532.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsAntibody FormationAutoantibodiesB-LymphocytesCase-Control StudiesCytokinesDisease Models, AnimalFemaleHumansImmunoglobulinsInterferon Type IInterferon-gammaInterleukinsLupus Erythematosus, SystemicMaleMice, Inbred MRL lprMiddle AgedRNA-SeqSTAT4 Transcription FactorT Follicular Helper CellsConceptsSystemic lupus erythematosusTfh-like cellsTfh cellsIL-21Human lupusDisease activityCytokine productionSTAT4 activationImmunoglobulin productionPathogenic B cell responsesCourse of lupusClinical disease activityT cell secretionLupus-prone miceHealthy control subjectsCourse of diseaseB cell responsesCytokine interleukin-21Potential therapeutic targetType I IFNB cell maturationSLE patientsPathogenic cytokinesLupus erythematosusInterleukin-21
2019
T 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 Research
2018
Single-cell RNA sequencing unveils an IL-10-producing helper subset that sustains humoral immunity during persistent infection
Xin G, Zander R, Schauder DM, Chen Y, Weinstein JS, Drobyski WR, Tarakanova V, Craft J, Cui W. Single-cell RNA sequencing unveils an IL-10-producing helper subset that sustains humoral immunity during persistent infection. Nature Communications 2018, 9: 5037. PMID: 30487586, PMCID: PMC6261948, DOI: 10.1038/s41467-018-07492-4.Peer-Reviewed Original ResearchConceptsCD4 T cellsIL-10Humoral immunityT cellsTfh cellsIL-10-expressing CD4 T cellsViral infectionAntiviral T cell responsesAcute LCMV infectionDouble reporter miceChronic viral infectionsCytokine IL-10T cell responsesPersistent viral infectionIL-10 signalingGerminal center reactionSingle-cell RNA-sequencing approachLCMV infectionHelper subsetsTh1 cellsChronic infectionInflammatory functionsViral controlPersistent infectionCell responsesHuman 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
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 Factors
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 responseThe 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 cellsPPARγ 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 deletionMiceB 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 display