2024
The amalgam of naive CD4+ T cell transcriptional states is reconfigured by helminth infection to dampen the amplitude of the immune response
Even Z, Meli A, Tyagi A, Vidyarthi A, Briggs N, de Kouchkovsky D, Kong Y, Wang Y, Waizman D, Rice T, De Kumar B, Wang X, Palm N, Craft J, Basu M, Ghosh S, Rothlin C. The amalgam of naive CD4+ T cell transcriptional states is reconfigured by helminth infection to dampen the amplitude of the immune response. Immunity 2024, 57: 1893-1907.e6. PMID: 39096910, PMCID: PMC11421571, DOI: 10.1016/j.immuni.2024.07.006.Peer-Reviewed Original ResearchT cell receptorImmune responseNaive CD4<sup>+</sup> T cellsCD4<sup>+</sup> T cellsIFN-IHelminth infectionsNippostrongylus brasiliensis infectionDecreased immune responseType I interferonNaive TT cellsMemory-likeUnrelated antigensTranscriptional changesExtracellular matrixSPF miceCell receptorsI interferonGerm-freeResponse to certain environmental cuesInfectionMiceFunctional changesCell transcriptional statesTranscriptional heterogeneity
2023
HIF-1 regulates pathogenic cytotoxic T cells in lupus skin disease
Little A, Chen P, Vesely M, Khan R, Fiedler J, Garritano J, Islam F, McNiff J, Craft J. HIF-1 regulates pathogenic cytotoxic T cells in lupus skin disease. JCI Insight 2023, 8: e166076. PMID: 37526979, PMCID: PMC10543720, DOI: 10.1172/jci.insight.166076.Peer-Reviewed Original ResearchConceptsCutaneous lupus erythematosusLupus skin diseaseT cellsSkin diseasesCytotoxic signatureInflammatory infiltrateHIF-1Tissue damageKidney-infiltrating T cellsSkin-infiltrating T cellsAutoimmune skin diseaseHIF-1 inhibitionSkin tissue damageLupus erythematosusSystemic diseaseTissue inflammationGranzyme BMouse modelInflammatory gene programDiseaseProtein levelsInfiltratesSkin environmentGene programPresent studyT follicular helper cells in cancer, tertiary lymphoid structures, and beyond
Cui C, Craft J, Joshi N. T follicular helper cells in cancer, tertiary lymphoid structures, and beyond. Seminars In Immunology 2023, 69: 101797. PMID: 37343412, DOI: 10.1016/j.smim.2023.101797.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsTumor-associated tertiary lymphoid structuresFollicular helper cellsCD8 T cellsTertiary lymphoid structuresSecondary lymphoid organsT cellsHelper cellsLymphoid structuresImmune cellsB cellsCD4 T follicular helper cellsT Follicular Helper CellsTumor-infiltrating immune cellsCurrent immunotherapy regimensCheckpoint blockade immunotherapyCD4 T cellsImmune cell componentsLimited response rateFunctional immune cellsNovel therapeutic targetPotential therapeutic benefitT cell-B cell interactionsBlockade immunotherapyImmunotherapy regimensLymphoid organsAP-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
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 ResearchConceptsTfh-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 nomenclatureCytokinesImmunityAntibodiesT Follicular Regulatory Cells: Choreographers of Productive Germinal Center Responses
Lu Y, Craft J. T Follicular Regulatory Cells: Choreographers of Productive Germinal Center Responses. Frontiers In Immunology 2021, 12: 679909. PMID: 34177925, PMCID: PMC8222975, DOI: 10.3389/fimmu.2021.679909.Peer-Reviewed Original ResearchConceptsTfr cellsTreg cellsHumoral immunityGerminal centersAntigen-specific B cell responsesFollicular helper cellsFollicular regulatory (Tfr) cellsB cell folliclesRegulatory T cellsB cell autoreactivityB cell responsesGerminal center responseB cell toleranceVaccine design strategiesTranscription factor Bcl6Regulatory cellsHelper cellsImmune homeostasisProductive immunityT cellsViral infectionCenter responseCell responsesGC responseImmune challenge
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 glycoproteinsKidney tissue hypoxia dictates T cell–mediated injury in murine lupus nephritis
Chen PM, Wilson PC, Shyer JA, Veselits M, Steach HR, Cui C, Moeckel G, Clark MR, Craft J. Kidney tissue hypoxia dictates T cell–mediated injury in murine lupus nephritis. Science Translational Medicine 2020, 12 PMID: 32269165, PMCID: PMC8055156, DOI: 10.1126/scitranslmed.aay1620.Peer-Reviewed Original ResearchConceptsHypoxia-inducible factor-1Lupus nephritisT cellsTissue hypoxiaT-cell-mediated injuryCell-mediated injuryHIF-1 blockadeKidney tissue hypoxiaSystemic lupus erythematosusHuman lupus nephritisMurine lupus nephritisRenal injuryAutoimmune injuryLupus erythematosusAutoimmune diseasesImmune cellsRenal tissueMurine modelTissue damageMore hypoxicNephritisInjuryLow oxygen tensionOxygen tensionFactor 1
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
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 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 FactorsThe TAM family receptor tyrosine kinase TYRO3 is a negative regulator of type 2 immunity
Chan PY, Carrera Silva EA, De Kouchkovsky D, Joannas LD, Hao L, Hu D, Huntsman S, Eng C, Licona-Limón P, Weinstein JS, Herbert DR, Craft JE, Flavell RA, Repetto S, Correale J, Burchard EG, Torgerson DG, Ghosh S, Rothlin CV. The TAM family receptor tyrosine kinase TYRO3 is a negative regulator of type 2 immunity. Science 2016, 352: 99-103. PMID: 27034374, PMCID: PMC4935984, DOI: 10.1126/science.aaf1358.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAnimalsAsthmaBlood ProteinsDendritic CellsDisease Models, AnimalGene Knockout TechniquesHost-Parasite InteractionsHumansImmunity, InnateInterleukin-4MiceMice, Inbred C57BLMice, KnockoutNippostrongylusProtein SPyroglyphidaeReceptor Protein-Tyrosine KinasesStrongylida InfectionsT-LymphocytesConceptsType 2 immunityType 2 responsesType 2 cytokinesHuman dendritic cellsInnate immune cellsDendritic cellsAllergic diseasesImmune cellsT cellsAdaptive immunityInterleukin-4Host responseFunctional neutralizationGenetic ablationReceptor tyrosine kinasesImmunityProtective functionTyro3Tyrosine kinaseNegative regulatorPROS1CellsResponseCytokinesDiseaseThe multifaceted role of CD4+ T cells in CD8+ T cell memory
Laidlaw BJ, Craft JE, Kaech SM. The multifaceted role of CD4+ T cells in CD8+ T cell memory. Nature Reviews Immunology 2016, 16: 102-111. PMID: 26781939, PMCID: PMC4860014, DOI: 10.1038/nri.2015.10.Peer-Reviewed Original ResearchConceptsT cell responsesT cell poolDendritic cellsT cell helpT cellsMemory CD8Cell helpCell responsesSuppression of DCTissue-resident memory CD8Regulatory T cellsT cell memoryCell poolSuppression of TNFApoptosis-inducing ligandEffector CD4Treg cellsFunctional CD8IL-21Primary CD8Protective immunityInterleukin-15Secondary responsivenessChronic infectionIL-2
2015
IL-21 Promotes Pulmonary Fibrosis through the Induction of Profibrotic CD8+ T Cells
Brodeur TY, Robidoux TE, Weinstein JS, Craft J, Swain SL, Marshak-Rothstein A. IL-21 Promotes Pulmonary Fibrosis through the Induction of Profibrotic CD8+ T Cells. The Journal Of Immunology 2015, 195: 5251-5260. PMID: 26519529, PMCID: PMC4655158, DOI: 10.4049/jimmunol.1500777.Peer-Reviewed Original ResearchA Critical Role of IL-21-Induced BATF in Sustaining CD8-T-Cell-Mediated Chronic Viral Control
Xin G, Schauder DM, Lainez B, Weinstein JS, Dai Z, Chen Y, Esplugues E, Wen R, Wang D, Parish IA, Zajac AJ, Craft J, Cui W. A Critical Role of IL-21-Induced BATF in Sustaining CD8-T-Cell-Mediated Chronic Viral Control. Cell Reports 2015, 13: 1118-1124. PMID: 26527008, PMCID: PMC4859432, DOI: 10.1016/j.celrep.2015.09.069.Peer-Reviewed Original ResearchConceptsCD8 T cellsChronic viral infectionsBATF expressionT cellsIL-21Chronic infectionEffector functionsViral infectionCD8 T cell effector functionsAnti-viral effector functionsCD8 T cell responsesCD8 T cell immunityT cell effector functionT cell immunityCD4 T cellsT cell responsesCell effector functionsT cell persistenceT cell maintenanceBlimp-1 expressionCD8 responsesCD4 helpCell immunityViral controlTranscription factor expressionThe 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 balance