2025
Single cell analysis identifies distinct CD4 + T cells associated with the pathobiology of pediatric obesity related asthma
Thompson D, Wabara Y, Duran S, Reichenbach A, Chen L, Collado K, Yon C, Greally DMed J, Rastogi D. Single cell analysis identifies distinct CD4 + T cells associated with the pathobiology of pediatric obesity related asthma. Scientific Reports 2025, 15: 6844. PMID: 40000680, PMCID: PMC11861978, DOI: 10.1038/s41598-025-88423-4.Peer-Reviewed Original ResearchConceptsCD4+ T cellsT cell subtypesT cellsSteroid resistanceTh1 inflammationObese asthmaTh1 responseCentral memory T cellsObese asthma phenotypeEffector T cellsMemory T cellsObesity-related asthmaCD4+ T cell subtypesPediatric obesity-related asthmaT helper 1Healthy-weight controlsPulmonary function deficitsCD4Th1Asthma phenotypesGlucocorticoid receptorSingle-cell transcriptomicsFunctional deficitsInflammationSteroidsDecreased T helper 1 cell function underlies recurrent sinopulmonary infections in the 17q12 deletion syndrome
Shin J, Shin H, Gutierrez A, Yoo N, Par-Young J, Osmani L, Shin M, Sanchez-Lara P, Bucala R, Soffer G, Kang I. Decreased T helper 1 cell function underlies recurrent sinopulmonary infections in the 17q12 deletion syndrome. EBioMedicine 2025, 112: 105578. PMID: 39891996, PMCID: PMC11840234, DOI: 10.1016/j.ebiom.2025.105578.Peer-Reviewed Original ResearchConceptsCD4<sup>+</sup> T cellsRecurrent sinopulmonary infectionsT cell functionRNA-seq analysisT cellsHealthy controlsSinopulmonary infectionsRNA-seqT-betIFN-gFrequency of CD4<sup>+</sup> T cellsCD4<sup>+</sup> T cell functionTh1 transcription factor T-betDeletion syndromeFlow cytometryCompared to age-matched healthy controlsTranscription factor T-betDecreased T-betUrinary tract abnormalitiesAge-matched healthy controlsMultiplex assayDownstream effector cytokinesEffector cytokinesRecurrent infectionsTh17 cytokines
2024
Neuropeptide signalling orchestrates T cell differentiation
Hou Y, Sun L, LaFleur M, Huang L, Lambden C, Thakore P, Geiger-Schuller K, Kimura K, Yan L, Zang Y, Tang R, Shi J, Barilla R, Deng L, Subramanian A, Wallrapp A, Choi H, Kye Y, Ashenberg O, Schiebinger G, Doench J, Chiu I, Regev A, Sharpe A, Kuchroo V. Neuropeptide signalling orchestrates T cell differentiation. Nature 2024, 635: 444-452. PMID: 39415015, PMCID: PMC11951087, DOI: 10.1038/s41586-024-08049-w.Peer-Reviewed Original ResearchMeSH KeywordsActivating Transcription Factor 3AnimalsCalcitonin Gene-Related PeptideCalcitonin Receptor-Like ProteinCell DifferentiationCyclic AMP Response Element-Binding ProteinFemaleMaleMiceMice, Inbred C57BLReceptor Activity-Modifying Protein 3Signal TransductionSTAT1 Transcription FactorTh1 CellsTh2 CellsConceptsT helper type 1Acute viral infectionActivating transcription factor 3Th1 cell differentiationCAMP response element-binding proteinViral infectionCell differentiationNeuropeptide CGRPFate determinationT cellsCD8+ T cell responsesDifferentiation of Th2 cellsIn vitro polarizationT cell fate determinationT cell responsesTh1 cell responsesCell fate determinationIn vivo CRISPR screeningDownstream cAMP response element-binding proteinT cell differentiationT helper cell differentiationIn vivo differentiationResponse element-binding proteinElement-binding proteinNeuroimmune circuitsBACH2 regulates diversification of regulatory and proinflammatory chromatin states in TH17 cells
Thakore P, Schnell A, Huang L, Zhao M, Hou Y, Christian E, Zaghouani S, Wang C, Singh V, Singaraju A, Krishnan R, Kozoriz D, Ma S, Sankar V, Notarbartolo S, Buenrostro J, Sallusto F, Patsopoulos N, Rozenblatt-Rosen O, Kuchroo V, Regev A. BACH2 regulates diversification of regulatory and proinflammatory chromatin states in TH17 cells. Nature Immunology 2024, 25: 1395-1410. PMID: 39009838, DOI: 10.1038/s41590-024-01901-1.Peer-Reviewed Original ResearchConceptsTransposase-accessible chromatin sequencingSingle-cell RNA sequencingTh17 heterogeneitySingle-cell assaysScATAC-seqChromatin landscapeChromatin stateChromatin sequencingRegulatory networksScRNA-seqTh17 cell pathogenicityHuman geneticsIn vivoRNA sequencingChromatin configurationRegulatory pathwaysTissue homeostasisCell statesCells in vitroBach2ChromatinSequenceCellsType 1 helper T (Th1) cellsCD4+ T cell subsetsExpression of Transcriptional Factors of T Helper Differentiation (T-bet, GATA-3, RORγt, and FOXP3), MIF Receptors (CD44, CD74, CXCR2, 4, 7), and Th1, Th2, and Th17 Cytokines in PBMC from Control Subjects and Rheumatoid Arthritis Patients
Zerpa-Hernández D, García-Chagollán M, Sánchez-Zuno G, García-Arellano S, Hernández-Bello J, Hernández-Palma L, Cerpa-Cruz S, Martinez-Bonilla G, Nicoletti F, Muñoz-Valle J. Expression of Transcriptional Factors of T Helper Differentiation (T-bet, GATA-3, RORγt, and FOXP3), MIF Receptors (CD44, CD74, CXCR2, 4, 7), and Th1, Th2, and Th17 Cytokines in PBMC from Control Subjects and Rheumatoid Arthritis Patients. 2024, 24: 1169-1182. PMID: 37807647, DOI: 10.2174/0115665240260976230925095330.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsMacrophage migration inhibitory factorT CD4+ lymphocytesMIF receptorRA patientsControl subjectsCS groupTh17 cytokinesRheumatoid arthritisElevated levels of pro-inflammatory cytokinesActivity of Foxp3Multiplex bead analysisLevels of pro-inflammatory cytokinesExpression of CXCR7Expression of CD74Expression of GATA3Levels of cytokinesT helper differentiationBlood mononuclear cellsPro-inflammatory cytokinesMigration inhibitory factorDevelopment of rheumatoid arthritisRheumatoid arthritis patientsProfile cytokinesTh17 responses
2023
Cutting Edge: Serpine1 Negatively Regulates Th1 Cell Responses in Experimental Autoimmune Encephalomyelitis.
Akbar I, Tang R, Baillargeon J, Roy A, Doss P, Zhu C, Kuchroo V, Rangachari M. Cutting Edge: Serpine1 Negatively Regulates Th1 Cell Responses in Experimental Autoimmune Encephalomyelitis. The Journal Of Immunology 2023, 211: 1762-1766. PMID: 37909848, DOI: 10.4049/jimmunol.2300526.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalomyelitisTh1 cellsTim-3Autoimmune encephalomyelitisTh1 cell responsesCell cytokine productionInhibitors of IFNExpression of IFNEAE phenotypeCytokine productionMild diseaseInhibitory receptorsLAG-3T cellsEnhanced severityKnockout miceCell responsesReduced expressionEncephalomyelitis
2021
mTORC1 Signaling Regulates Proinflammatory Macrophage Function and Metabolism.
Collins S, Oh M, Sun I, Chan-Li Y, Zhao L, Powell J, Horton M. mTORC1 Signaling Regulates Proinflammatory Macrophage Function and Metabolism. The Journal Of Immunology 2021, 207: 913-922. PMID: 34290107, DOI: 10.4049/jimmunol.2100230.Peer-Reviewed Original ResearchConceptsKey regulatorImmune cell functionEnhanced histone acetylationCell functionRapid energy sourceClass III histoneDifferentiation of macrophagesHistone acetylationMacrophage functionMTORC1 signalingCellular metabolismOxidative phosphorylationCell metabolismMTOR signalingGlycolytic metabolismAntimicrobial compoundsGenetic deletionM2 macrophagesMouse macrophagesProper wound healingMetabolic programmingSignificant defectsM1 functionImmune cell metabolismSignalingBronchoalveolar Lavage Fluid Reflects a TH1-CD21low B-Cell Interaction in CVID-Related Interstitial Lung Disease
Friedmann D, Unger S, Keller B, Rakhmanov M, Goldacker S, Zissel G, Frye B, Schupp J, Prasse A, Warnatz K. Bronchoalveolar Lavage Fluid Reflects a TH1-CD21low B-Cell Interaction in CVID-Related Interstitial Lung Disease. Frontiers In Immunology 2021, 11: 616832. PMID: 33613543, PMCID: PMC7892466, DOI: 10.3389/fimmu.2020.616832.Peer-Reviewed Original ResearchConceptsInterstitial lung diseaseCommon variable immunodeficiencyBAL fluidB cellsLung diseaseT cellsImmune dysregulationBronchoalveolar lavageHealthy donorsClass-switched memory B cellsLymphocytic interstitial lung diseaseProgressive interstitial lung diseaseLevels of BAFFLike cell subsetSystemic immune dysregulationRegulatory T cellsVideo-assisted thoracoscopyBronchoalveolar lavage fluidT cell populationsPotential immune mechanismsLevels of APRILMemory B cellsB cell interactionsFlow cytometric profilingPotential treatment target
2020
Contribution of systemic and airway immune responses to pediatric obesity-related asthma
Chen L, Collado K, Rastogi D. Contribution of systemic and airway immune responses to pediatric obesity-related asthma. Paediatric Respiratory Reviews 2020, 37: 3-9. PMID: 32253127, PMCID: PMC8477371, DOI: 10.1016/j.prrv.2020.02.005.Peer-Reviewed Original ResearchConceptsObesity-related asthmaImmune responseDifferentiation to Th1 cellsTh cell responsesAirway immune responsesNormal-weight childrenPediatric obesity-related asthmaTh1 cellsObese childrenCytokine productionUpregulation of genesChildhood obesityNon-allergicCdc42 pathwayCell physiologyCell responsesEpigenetic mechanismsDisease burdenAsthmaAirwayObesityCdc42DiseasePathwayChildren
2019
Distinct 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 functionsTranscriptomic profiles conducive to immune-mediated tumor rejection in human breast cancer skin metastases treated with Imiquimod
Rozenblit M, Hendrickx W, Heguy A, Chiriboga L, Loomis C, Ray K, Darvishian F, Egeblad M, Demaria S, Marincola FM, Bedognetti D, Adams S. Transcriptomic profiles conducive to immune-mediated tumor rejection in human breast cancer skin metastases treated with Imiquimod. Scientific Reports 2019, 9: 8572. PMID: 31189943, PMCID: PMC6561945, DOI: 10.1038/s41598-019-42784-9.Peer-Reviewed Original ResearchConceptsBreast cancer skin metastasesBreast cancer metastasisSkin metastasesImmune responsePost-treatment tumor samplesCancer metastasisReceptor 7 agonistStrong T-helperDurable clinical responsesImmune effector functionsBasal cell carcinomaRobust immune responseTopical imiquimodClinical responseT helperTumor rejectionCell carcinomaCytotoxic functionTranscriptomic profilesTumor regressionClinical trialsAntigen presentationT cellsImiquimodTumor destructionLocal Delivery of Regulatory T Cells Promotes Corneal Allograft Survival
Shao C, Chen Y, Nakao T, Amouzegar A, Yin J, Tahvildari M, Lužnik Z, Chauhan S, Dana R. Local Delivery of Regulatory T Cells Promotes Corneal Allograft Survival. Transplantation 2019, 103: 182-190. PMID: 30247445, PMCID: PMC6309927, DOI: 10.1097/tp.0000000000002442.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAllograftsAnimalsAntigen-Presenting CellsChemotaxis, LeukocyteCorneaCorneal TransplantationCytokinesGraft SurvivalGreen Fluorescent ProteinsKineticsLymph NodesLymphocyte ActivationMaleMice, Inbred BALB CMice, Inbred C57BLMice, TransgenicT-Lymphocytes, RegulatoryTh1 CellsConceptsDraining lymph nodesTreg cellsAntigen-presenting cellsAllograft survivalIL-10Mature antigen-presenting cellsLong-term allograft survivalCorneal allograft recipientsCorneal allograft survivalTGF-bExpression of IFN-gCell-based immunotherapyLevels of IL-10Conventional T cellsPromote transplant survivalGFP transgenic miceCell-based modalitiesExpression of IFNGHost immune responseSuppress host immune responsesEnzyme-linked immunosorbent assayIpsilateral corneaTh1 frequencyReverse transcription polymerase chain reactionCorneal transplantation
2018
Distinct Regulation of Th17 and Th1 Cell Differentiation by Glutaminase-Dependent Metabolism
Johnson M, Wolf M, Madden M, Andrejeva G, Sugiura A, Contreras D, Maseda D, Liberti M, Paz K, Kishton R, Johnson M, de Cubas A, Wu P, Li G, Zhang Y, Newcomb D, Wells A, Restifo N, Rathmell W, Locasale J, Davila M, Blazar B, Rathmell J. Distinct Regulation of Th17 and Th1 Cell Differentiation by Glutaminase-Dependent Metabolism. Cell 2018, 175: 1780-1795.e19. PMID: 30392958, PMCID: PMC6361668, DOI: 10.1016/j.cell.2018.10.001.Peer-Reviewed Original ResearchConceptsCell differentiationDistinct metabolic programsAltered chromatin accessibilityTricarboxylic acid cycleChromatin accessibilityEpigenetic reactionsCell activationMetabolic programsGene expressionDistinct regulationAcid cycleGLS inhibitionTh1 cellsGlutamine metabolismDistinct rolesImpaired differentiationElevated functionEffector cell differentiationDifferentiationTh1 cell differentiationCell numberCellsCD4 Th1Th17 cellsInflammatory diseasesFingolimod modulates T cell phenotype and regulatory T cell plasticity in vivo
Dominguez-Villar M, Raddassi K, Danielsen AC, Guarnaccia J, Hafler DA. Fingolimod modulates T cell phenotype and regulatory T cell plasticity in vivo. Journal Of Autoimmunity 2018, 96: 40-49. PMID: 30122421, PMCID: PMC7882197, DOI: 10.1016/j.jaut.2018.08.002.Peer-Reviewed Original ResearchConceptsT cellsMultiple sclerosisT cell effector phenotypeRelapsing-remitting multiple sclerosisRegulatory T cell populationTh1-like phenotypeRegulatory T cellsPro-inflammatory cytokinesT-cell phenotypeT cell populationsExpression of Th1Immune cell functionRegulatory T cell plasticityT cell plasticityCentral nervous systemExpression of markersCell migratory capacityImportant immunomodulatory functionsExcessive Th1Fingolimod treatmentExhaustion markersTh17 cytokinesEffector phenotypeLymph nodesSerum levelsRegulation of chitinase-3-like-1 in T cell elicits Th1 and cytotoxic responses to inhibit lung metastasis
Kim DH, Park HJ, Lim S, Koo JH, Lee HG, Choi JO, Oh JH, Ha SJ, Kang MJ, Lee CM, Lee CG, Elias JA, Choi JM. Regulation of chitinase-3-like-1 in T cell elicits Th1 and cytotoxic responses to inhibit lung metastasis. Nature Communications 2018, 9: 503. PMID: 29403003, PMCID: PMC5799380, DOI: 10.1038/s41467-017-02731-6.Peer-Reviewed Original ResearchConceptsT cellsLung metastasesTh1 cellsCHI3L1 expressionFunction of CHI3L1Type 2 inflammationAnti-tumor immunityMelanoma lung metastasisActivated T cellsElicit Th1CTL responsesEnhanced Th1Th2 cellsTherapeutic targetClinical implicationsCytotoxic responseTh1MetastasisTCR stimulationCHI3L1Peptide-siRNA complexLungCellsNegative regulatorImmunity genes
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 survivalLocal and Systemic CD4+ T Cell Exhaustion Reverses with Clinical Resolution of Pulmonary Sarcoidosis
Hawkins C, Shaginurova G, Shelton DA, Herazo-Maya JD, Oswald-Richter KA, Rotsinger JE, Young A, Celada LJ, Kaminski N, Sevin C, Drake WP. Local and Systemic CD4+ T Cell Exhaustion Reverses with Clinical Resolution of Pulmonary Sarcoidosis. Journal Of Immunology Research 2017, 2017: 3642832. PMID: 29234685, PMCID: PMC5695030, DOI: 10.1155/2017/3642832.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedApoptosisCD4-Positive T-LymphocytesCell ProliferationCells, CulturedClonal AnergyCytokinesDisease ProgressionFemaleGene Expression RegulationHumansLymphocyte ActivationMaleMiddle AgedProgrammed Cell Death 1 ReceptorReceptors, Antigen, T-Cell, alpha-betaSarcoidosis, PulmonaryTh1 CellsYoung AdultConceptsT cell exhaustionTh1 cytokine expressionPD-1 expressionCell exhaustionCytokine expressionT cellsHealthy controlsInhibitory cell surface receptorsT cell immune functionTh1 immune responseChronic antigenic stimulationCell immune functionProliferative capacityT cell functionSarcoidosis subjectsSystemic CD4Pulmonary sarcoidosisDisease resolutionProgressive diseaseClinical resolutionCytokine productionAntigenic stimulationDisease progressionImmune responseCD4Transcriptome profiles in sarcoidosis and their potential role in disease prediction
Schupp JC, Vukmirovic M, Kaminski N, Prasse A. Transcriptome profiles in sarcoidosis and their potential role in disease prediction. Current Opinion In Pulmonary Medicine 2017, 23: 487-492. PMID: 28590292, PMCID: PMC5637542, DOI: 10.1097/mcp.0000000000000403.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsGenome-wide expression studiesWide expression studiesTranscriptome profilesTranscriptomic dataRNA sequencingExpression studiesGene expressionMolecular mechanismsLarge prospective followTh1 immune responseTranscriptomeNonnecrotizing granulomasProspective followSystemic diseaseDisease progressionTreatment outcomesImmune responseSarcoidosisPotential roleControl tissuesProgressive sarcoidosisKey roleDiseaseTranscriptomicsGranulomasB7-DC (PD-L2) costimulation of CD4+ T-helper 1 response via RGMb
Nie X, Chen W, Zhu Y, Huang B, Yu W, Wu Z, Guo S, Zhu Y, Luo L, Wang S, Chen L. B7-DC (PD-L2) costimulation of CD4+ T-helper 1 response via RGMb. Cellular & Molecular Immunology 2017, 15: 888-897. PMID: 28479601, PMCID: PMC6207567, DOI: 10.1038/cmi.2017.17.Peer-Reviewed Original ResearchConceptsRepulsive guidance molecule bT cell responsesB7-DCPD-1T cellsB7-DC/PDCoinhibitory receptor PD-1T helper 1 responseTh2-mediated asthmaSmall airway inflammationReceptor PD-1T cell inhibitionExperimental mouse modelNaive mouse T cellsMouse T cellsAirway inflammationTh1 polarizationTh1 responseDendritic cellsLung pathologyMouse modelCostimulatory functionCostimulatory receptorsCD4Costimulation
2016
Sex-Based Selectivity of PPARγ Regulation in Th1, Th2, and Th17 Differentiation
Park HJ, Park HS, Lee JU, Bothwell AL, Choi JM. Sex-Based Selectivity of PPARγ Regulation in Th1, Th2, and Th17 Differentiation. International Journal Of Molecular Sciences 2016, 17: 1347. PMID: 27548145, PMCID: PMC5000743, DOI: 10.3390/ijms17081347.Peer-Reviewed Original ResearchConceptsEffector T cell differentiationT cellsT cell differentiationAdaptive immunityFemale T cellsMale T cellsPeroxisome proliferator-activated receptor gammaIL-17 productionDifferentiation of Th1PPARγ agonist pioglitazoneProliferator-activated receptor gammaNaïve T cellsSplenic T cellsMouse splenic T cellsImportant immune regulatorPioglitazone treatmentTfh responsesTh17 cellsAgonist pioglitazoneTreg functionAutoimmune diseasesEstrogen exposureImmune regulatorsCell differentiationTh1
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