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, PMCID: PMC11614491, 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 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 subsetsTIGIT predominantly regulates the immune response via regulatory T cells
Kurtulus S, Sakuishi K, Ngiow S, Joller N, Tan D, Teng M, Smyth M, Kuchroo V, Anderson A. TIGIT predominantly regulates the immune response via regulatory T cells. Journal Of Clinical Investigation 2024, 134: e183278. PMID: 38949028, PMCID: PMC11213499, DOI: 10.1172/jci183278.Peer-Reviewed Original ResearchCharting the cellular biogeography in colitis reveals fibroblast trajectories and coordinated spatial remodeling
Cadinu P, Sivanathan K, Misra A, Xu R, Mangani D, Yang E, Rone J, Tooley K, Kye Y, Bod L, Geistlinger L, Lee T, Mertens R, Ono N, Wang G, Sanmarco L, Quintana F, Anderson A, Kuchroo V, Moffitt J, Nowarski R. Charting the cellular biogeography in colitis reveals fibroblast trajectories and coordinated spatial remodeling. Cell 2024, 187: 2010-2028.e30. PMID: 38569542, PMCID: PMC11017707, DOI: 10.1016/j.cell.2024.03.013.Peer-Reviewed Original ResearchConceptsMultiplexed error-robust fluorescence in situ hybridizationFluorescence in situ hybridizationSpatial organizationCell-cell interactionsDiverse cell populationsHealthy gutMouse colitis modelExpression profilesBiogeographyGutNon-immune cellsGut inflammationSpatial remodelingInflammation-associated fibroblastsTissue neighborhoodsInflammation-induced remodelingCell populationsFibroblastsImmune cellsCellsColitis modelUlcerative colitisFibroblastic originStage progressionExpressionA mouse DRG genetic toolkit reveals morphological and physiological diversity of somatosensory neuron subtypes
Qi L, Iskols M, Shi D, Reddy P, Walker C, Lezgiyeva K, Voisin T, Pawlak M, Kuchroo V, Chiu I, Ginty D, Sharma N. A mouse DRG genetic toolkit reveals morphological and physiological diversity of somatosensory neuron subtypes. Cell 2024, 187: 1508-1526.e16. PMID: 38442711, PMCID: PMC10947841, DOI: 10.1016/j.cell.2024.02.006.Peer-Reviewed Original Research
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