2024
Transcription factor TCF1 binds to RORγt and orchestrates a regulatory network that determines homeostatic Th17 cell state
Mangani D, Subramanian A, Huang L, Cheng H, Krovi S, Wu Y, Yang D, Moreira T, Escobar G, Schnell A, Dixon K, Krishnan R, Singh V, Sobel R, Weiner H, Kuchroo V, Anderson A. Transcription factor TCF1 binds to RORγt and orchestrates a regulatory network that determines homeostatic Th17 cell state. Immunity 2024, 57: 2565-2582.e6. PMID: 39447575, DOI: 10.1016/j.immuni.2024.09.017.Peer-Reviewed Original ResearchConceptsCell statesRegulatory networksSpectrum of cell statesTh17 cellsTranscription factor TPro-inflammatory Th17 cellsHomeostatic tissue functionReceptor signalingMature T cellsAutoimmune tissue damageInterleukin (IL)-23Controlling tissue inflammationPro-inflammatory functionsPro-inflammatory cellsConditional deletionDevelopment of therapiesRestore homeostasisPro-inflammatory potentialTCF1T-helperT cellsRORgtTissue inflammationCellsInflammatory diseasesNeuropeptide 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, 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 circuitsOncogene induced TIM-3 ligand expression dictates susceptibility to anti-TIM-3 therapy in mice
Talvard-Balland N, Braun L, Dixon K, Zwick M, Engel H, Hartmann A, Duquesne S, Penter L, Andrieux G, Rindlisbacher L, Acerbis A, Ehmann J, Köllerer C, Ansuinelli M, Rettig A, Moschallski K, Apostolova P, Brummer T, Illert A, Schramm M, Cheng Y, Köttgen A, Duyster J, Menssen H, Ritz J, Blazar B, Boerries M, Graeff A, Sariipek N, van Galen P, Buescher J, Cabezas-Wallscheid N, Pahl H, Pearce E, Soiffer R, Wu C, Vago L, Becher B, Köhler N, Wertheimer T, Kuchroo V, Zeiser R. Oncogene induced TIM-3 ligand expression dictates susceptibility to anti-TIM-3 therapy in mice. Journal Of Clinical Investigation 2024, 134: e177460. PMID: 38916965, PMCID: PMC11324309, DOI: 10.1172/jci177460.Peer-Reviewed Original ResearchAcute graft-versus-host diseaseAcute myeloid leukemiaPost-allo-HCTTim-3GVL effectLigand expressionGraft-versus-host diseaseAllogeneic hematopoietic cell transplantationCD8+ T cellsEnhanced GVL effectIFN-g productionLow ligand expressionTim-3 ligandAnti-PD-1TIM-3 blockadeAnti-Tim-3Hematopoietic cell transplantationSurvival of miceCells of patientsAllo-HCTLeukemia relapseCell transplantationCause of deathMyeloid leukemiaT cellsHuman regulatory memory B cells defined by expression of TIM-1 and TIGIT are dysfunctional in multiple sclerosis
Varghese J, Kaskow B, von Glehn F, Case J, Li Z, Julé A, Berdan E, Sui S, Hu Y, Krishnan R, Chitnis T, Kuchroo V, Weiner H, Baecher-Allan C. Human regulatory memory B cells defined by expression of TIM-1 and TIGIT are dysfunctional in multiple sclerosis. Frontiers In Immunology 2024, 15: 1360219. PMID: 38745667, PMCID: PMC11091236, DOI: 10.3389/fimmu.2024.1360219.Peer-Reviewed Original ResearchConceptsMemory B cell subsetsMemory B cellsB cell subsetsT cell activationB cellsT cellsMultiple sclerosisIL-17ATIM-1Levels of CD4+ T cell activationAllogeneic CD4+ T cellsRelapsing-remittingAssociated with response to therapyAnti-CD20 treated patientsCD4+ T cell activationDouble positive (DPCD4+ T cellsExpression of TIM-1Genes associated with T-cell activationInduction of inflammatory markersInduce T cell proliferationHuman memory B cellsLack of cell surface markersRegulatory B cellsExpression of genes associated with T-cell activationBeyond T cell exhaustion: TIM-3 regulation of myeloid cells
Dixon K, Lahore G, Kuchroo V. Beyond T cell exhaustion: TIM-3 regulation of myeloid cells. Science Immunology 2024, 9: eadf2223. PMID: 38457514, DOI: 10.1126/sciimmunol.adf2223.Peer-Reviewed Original ResearchConceptsT cell exhaustionTim-3CD8<sup>+</sup> T cellsImmune responseRegulation of myeloid cell functionT cell stemnessTim-3 regulationImmune checkpoint moleculesT cell immunoglobulinCell-extrinsic mechanismsMyeloid cell functionRegulation of myeloid cellsCheckpoint moleculesTreatment of cancerCD4<sup>+</sup>T cellsMyeloid cellsCell-intrinsicCell functionAutoimmunityAutoinflammationCancerImmunoglobulinLAG-3, TIM-3, and TIGIT: Distinct functions in immune regulation
Joller N, Anderson A, Kuchroo V. LAG-3, TIM-3, and TIGIT: Distinct functions in immune regulation. Immunity 2024, 57: 206-222. PMID: 38354701, PMCID: PMC10919259, DOI: 10.1016/j.immuni.2024.01.010.Peer-Reviewed Original ResearchConceptsLAG-3Tim-3Immune cellsRestraining T-cell responsesImmune checkpoint receptorsT cell responsesRegulation of immune cellsImmune cell typesApplication of therapyPotential tissue toxicityCheckpoint receptorsTissue toxicityT cellsClinical developmentImmune regulationTIGITCell responsesReceptorsCell typesClinicCellsTherapy
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 expressionEncephalomyelitisTargeting PGLYRP1 promotes antitumor immunity while inhibiting autoimmune neuroinflammation
Schnell A, Huang L, Regan B, Singh V, Vonficht D, Bollhagen A, Wang M, Hou Y, Bod L, Sobel R, Chihara N, Madi A, Anderson A, Regev A, Kuchroo V. Targeting PGLYRP1 promotes antitumor immunity while inhibiting autoimmune neuroinflammation. Nature Immunology 2023, 24: 1908-1920. PMID: 37828379, PMCID: PMC10864036, DOI: 10.1038/s41590-023-01645-4.Peer-Reviewed Original ResearchConceptsPeptidoglycan recognition protein 1T cellsMyeloid cellsGenetic deletionPotent antitumor immune responsesCo-inhibitory moleculesExperimental autoimmune encephalomyelitisAntitumor immune responseImmune checkpoint blockadePromising targetSuccessful treatment optionT cell functionCentral nervous systemT cell activationMultiple human cancersAutoimmune neuroinflammationAntitumor immunityAutoimmune encephalomyelitisCheckpoint blockadeCheckpoint moleculesEffector phenotypeAutoimmune diseasesProinflammatory moleculesTissue inflammationTreatment options