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 subsets
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