2023
Bulk and single-nucleus RNA sequencing highlight immune pathways induced in individuals during an Ixodes scapularis tick bite
Tang X, Lynn G, Cui Y, Cerny J, Arora G, Tomayko M, Craft J, Fikrig E. Bulk and single-nucleus RNA sequencing highlight immune pathways induced in individuals during an Ixodes scapularis tick bite. Infection And Immunity 2023, 91: e00282-23. PMID: 37846980, PMCID: PMC10652856, DOI: 10.1128/iai.00282-23.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceFeeding BehaviorGuinea PigsHumansIxodesRNA, Small NuclearTick BitesConceptsRNA sequencingSingle-nucleus RNA sequencingBulk RNA sequencingInterleukin-17 signalingPlatelet activation pathwaysLaboratory guinea pigsSnRNA-seqHippo signalingIndividual genesPeripheral bloodTick biteAdaptive immunityAnti-tick vaccinesGuidance pathwayImmune pathwaysNew biomarkersHost responseGuinea pigsHematophagous arthropodsHost defenseCell adhesionTick attachmentNovel insightsTick feedingPhysiological consequencesCutting Edge: IL-21 and Tissue-Specific Signals Instruct Tbet+CD11c+ B Cell Development following Viral Infection.
Song W, Sanchez G, Mayer D, Blackburn H, Chernova I, Flavell R, Weinstein J, Craft J. Cutting Edge: IL-21 and Tissue-Specific Signals Instruct Tbet+CD11c+ B Cell Development following Viral Infection. The Journal Of Immunology 2023, 210: 1861-1865. PMID: 37133336, PMCID: PMC10247523, DOI: 10.4049/jimmunol.2300027.Peer-Reviewed Original ResearchConceptsAge-associated B cellsIL-21Acute lymphocytic choriomeningitis virus infectionB cellsLymphocytic choriomeningitis virus infectionB cell activationHumoral immunityLymphoid organsVirus infectionMouse modelViral infectionB cell developmentCell activationLymphotoxin αVivo generationTissue-specific signalsInfectionDe novo generationOrgan contributionIFNTissue microenvironmentCell developmentLiverPivotal contributorStage-specific rolesAP-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
Spatial profiling of chromatin accessibility in mouse and human tissues
Deng Y, Bartosovic M, Ma S, Zhang D, Kukanja P, Xiao Y, Su G, Liu Y, Qin X, Rosoklija GB, Dwork AJ, Mann JJ, Xu ML, Halene S, Craft JE, Leong KW, Boldrini M, Castelo-Branco G, Fan R. Spatial profiling of chromatin accessibility in mouse and human tissues. Nature 2022, 609: 375-383. PMID: 35978191, PMCID: PMC9452302, DOI: 10.1038/s41586-022-05094-1.Peer-Reviewed Original ResearchConceptsChromatin accessibilityATAC-seqSpecific epigenetic landscapesChromatin accessibility profilingCell fate decisionsEpigenetic informationEpigenetic landscapeGenome scaleFate decisionsAccessible genomeCell identityEpigenetic underpinningsNext-generation sequencingGene regulatorsCell statesMouse embryosSpatial biologySpatial transcriptomicsCell typesCellular levelImmune cell typesDistinct organizationHuman tissuesProfilingSpatial profilingHigh-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-19PatientsDevelopment of Tbet- and CD11c-expressing B cells in a viral infection requires T follicular helper cells outside of germinal centers
Song W, Antao OQ, Condiff E, Sanchez GM, Chernova I, Zembrzuski K, Steach H, Rubtsova K, Angeletti D, Lemenze A, Laidlaw BJ, Craft J, Weinstein JS. Development of Tbet- and CD11c-expressing B cells in a viral infection requires T follicular helper cells outside of germinal centers. Immunity 2022, 55: 290-307.e5. PMID: 35090581, PMCID: PMC8965751, DOI: 10.1016/j.immuni.2022.01.002.Peer-Reviewed Original ResearchConceptsFollicular helper cellsB cellsGC B cellsHelper cellsMemory subsetsRobust recall responsesB cell subsetsGerminal center formationB cell generationAcute infectionCell subsetsRecall responsesTh1 cellsProximal deliveryCD11cGerminal centersIntegrin LFA-1Viral infectionAntibody productionVLA-4Splenic retentionLFA-1TbetBCL6 expressionInfection
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 functionCD4T 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 challengeType 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
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 glycoproteinsRepeat tick exposure elicits distinct immune responses in guinea pigs and mice
Kurokawa C, Narasimhan S, Vidyarthi A, Booth CJ, Mehta S, Meister L, Diktas H, Strank N, Lynn GE, DePonte K, Craft J, Fikrig E. Repeat tick exposure elicits distinct immune responses in guinea pigs and mice. Ticks And Tick-borne Diseases 2020, 11: 101529. PMID: 32993942, PMCID: PMC7530331, DOI: 10.1016/j.ttbdis.2020.101529.Peer-Reviewed Original ResearchConceptsGuinea pigsElicit distinct immune responsesDistinct immune responsesGuinea pig modelLocal blood flowImmune animalsInflammatory pathwaysTick rejectionMechanisms of resistanceImmune responseMouse modelVaccine candidatesBite siteBlood flowPig modelCoagulation pathwayComplement activationAcquired ResistanceProtective antigenTick detachmentTick proteinsBlood mealMiceTick infestationRNA sequencingKidney 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
Impaired ATM activation in B cells is associated with bone resorption in rheumatoid arthritis
Mensah KA, Chen JW, Schickel JN, Isnardi I, Yamakawa N, Vega-Loza A, Anolik JH, Gatti RA, Gelfand EW, Montgomery RR, Horowitz MC, Craft JE, Meffre E. Impaired ATM activation in B cells is associated with bone resorption in rheumatoid arthritis. Science Translational Medicine 2019, 11 PMID: 31748230, PMCID: PMC7167286, DOI: 10.1126/scitranslmed.aaw4626.Peer-Reviewed Original ResearchConceptsRheumatoid arthritisB cellsHealthy donor controlsGroup of patientsHumanized mouse modelImmature B cellsGene segment usageErosive diseaseRA pathophysiologyBone erosionBone lossBone resorptionHigh prevalenceRANKL productionBone densityMouse modelReceptor activatorBone marrowPatientsDonor controlsCD21Segment usageArthritisElevated frequencyAtaxia telangiectasiaIdentification 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 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 developmentDistinct modes of mitochondrial metabolism uncouple T cell differentiation and function
Bailis W, Shyer JA, Zhao J, Canaveras JCG, Al Khazal FJ, Qu R, Steach HR, Bielecki P, Khan O, Jackson R, Kluger Y, Maher LJ, Rabinowitz J, Craft J, Flavell RA. Distinct modes of mitochondrial metabolism uncouple T cell differentiation and function. Nature 2019, 571: 403-407. PMID: 31217581, PMCID: PMC6939459, DOI: 10.1038/s41586-019-1311-3.Peer-Reviewed Original ResearchConceptsMitochondrial citrate exportTerminal effector functionsMalate-aspartate shuttleCitrate exportHistone acetylationCell differentiationComplex ICellular biochemical compositionT cell differentiationSuccinate dehydrogenaseT cell activationExpression of genesElectron transport chainTricarboxylic acid cycleT cell receptor ligationAnabolic programTranscriptional remodellingTranscriptional programmingEpigenetic remodellingSignal transductionCell activationMetabolic reprogrammingCell statesDistinct modesEffector functionsT 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 responsesscFTD-seq: freeze-thaw lysis based, portable approach toward highly distributed single-cell 3′ mRNA profiling
Dura B, Choi JY, Zhang K, Damsky W, Thakral D, Bosenberg M, Craft J, Fan R. scFTD-seq: freeze-thaw lysis based, portable approach toward highly distributed single-cell 3′ mRNA profiling. Nucleic Acids Research 2018, 47: e16-e16. PMID: 30462277, PMCID: PMC6379653, DOI: 10.1093/nar/gky1173.Peer-Reviewed Original ResearchAnimalsCell LineFreezingGene Expression ProfilingHigh-Throughput Nucleotide SequencingHuman Umbilical Vein Endothelial CellsHumansLupus Erythematosus, SystemicMaleMelanoma, ExperimentalMiceOligonucleotide Array Sequence AnalysisRNA, MessengerSequence Analysis, RNASingle-Cell AnalysisT-LymphocytesWorkflow
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 survival