Featured Publications
A local regulatory T cell feedback circuit maintains immune homeostasis by pruning self-activated T cells
Wong H, Park K, Gola A, Baptista A, Miller C, Deep D, Lou M, Boyd L, Rudensky A, Savage P, Altan-Bonnet G, Tsang J, Germain R. A local regulatory T cell feedback circuit maintains immune homeostasis by pruning self-activated T cells. Cell 2021, 184: 3981-3997.e22. PMID: 34157301, PMCID: PMC8390950, DOI: 10.1016/j.cell.2021.05.028.Peer-Reviewed Original Research
2023
Inflammatory and interferon gene expression signatures in patients with mitochondrial disease
Warren E, Gordon-Lipkin E, Cheung F, Chen J, Mukherjee A, Apps R, Tsang J, Jetmore J, Schlein M, Kruk S, Lei Y, West A, McGuire P. Inflammatory and interferon gene expression signatures in patients with mitochondrial disease. Journal Of Translational Medicine 2023, 21: 331. PMID: 37208779, PMCID: PMC10199642, DOI: 10.1186/s12967-023-04180-w.Peer-Reviewed Original ResearchConceptsMTD patientsHealthy controlsMitochondrial dysfunctionAntiviral responseInterferon gene expression signatureChronic inflammatory disordersType I interferonCommon gene signaturePeripheral inflammationGene expression signaturesImmune dysregulationChronic inflammationMetabolic decompensationInflammatory disordersInterleukin-1βSymptom progressionT cellsInflammatory signalingMouse modelI interferonMitochondrial diseasePatientsTranslational evidenceMELAS patientsDysfunction
2021
Pre-existing chromatin accessibility and gene expression differences among naive CD4+ T cells influence effector potential
Rogers D, Sood A, Wang H, van Beek J, Rademaker T, Artusa P, Schneider C, Shen C, Wong D, Bhagrath A, Lebel M, Condotta S, Richer M, Martins A, Tsang J, Barreiro L, François P, Langlais D, Melichar H, Textor J, Mandl J. Pre-existing chromatin accessibility and gene expression differences among naive CD4+ T cells influence effector potential. Cell Reports 2021, 37: 110064. PMID: 34852223, DOI: 10.1016/j.celrep.2021.110064.Peer-Reviewed Original ResearchConceptsSingle-cell RNA sequencingGene expression differencesCell receptor signalingChromatin accessibilityLineage choiceTCR signal strengthCell chromatinTranscriptional differencesRNA sequencingExpression differencesReceptor signalingLandscape differencesEffector potentialEffector lineagesThymic developmentCellsNaive CD4Self-peptide MHCChromatinCognate antigenLineagesGenesSignalingTCR interactionsKey drivers
2020
Intravenous nanoparticle vaccination generates stem-like TCF1+ neoantigen-specific CD8+ T cells
Baharom F, Ramirez-Valdez RA, Tobin KKS, Yamane H, Dutertre CA, Khalilnezhad A, Reynoso GV, Coble VL, Lynn GM, Mulè MP, Martins AJ, Finnigan JP, Zhang XM, Hamerman JA, Bhardwaj N, Tsang JS, Hickman HD, Ginhoux F, Ishizuka AS, Seder RA. Intravenous nanoparticle vaccination generates stem-like TCF1+ neoantigen-specific CD8+ T cells. Nature Immunology 2020, 22: 41-52. PMID: 33139915, PMCID: PMC7746638, DOI: 10.1038/s41590-020-00810-3.Peer-Reviewed Original ResearchConceptsNeoantigen-specific CD8T cellsToll-like receptor 7/8 agonistQuality of CD8Stem-like TCF1T cell immunityStem-like CD8Superior antitumor responsesPersonalized cancer vaccinesStem-like genesStem-like cellsIntravenous vaccinationNanoparticle vaccinationAntitumor immunityCheckpoint blockadeCell immunityDendritic cellsAntitumor responseEffector cellsSubcutaneous immunizationCancer vaccinesVaccine parametersNeoantigen peptidesAntigen presentationNanoparticle vaccine
2019
Differential Expression of the Transcription Factor GATA3 Specifies Lineage and Functions of Innate Lymphoid Cells
Zhong C, Zheng M, Cui K, Martins A, Hu G, Li D, Tessarollo L, Kozlov S, Keller J, Tsang J, Zhao K, Zhu J. Differential Expression of the Transcription Factor GATA3 Specifies Lineage and Functions of Innate Lymphoid Cells. Immunity 2019, 52: 83-95.e4. PMID: 31882362, PMCID: PMC6962539, DOI: 10.1016/j.immuni.2019.12.001.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineageCells, CulturedGATA3 Transcription FactorInhibitor of Differentiation Protein 2Interleukin Receptor Common gamma SubunitMiceMice, Inbred C57BLMice, KnockoutNuclear Receptor Subfamily 1, Group F, Member 3Programmed Cell Death 1 ReceptorPromyelocytic Leukemia Zinc Finger ProteinStem CellsT-Lymphocyte SubsetsT-Lymphocytes, Helper-InducerConceptsILC progenitorsDifferential expressionTranscription factor PLZFTranscriptional regulator Id2Common progenitorLymphoid progenitorsGATA3 expressionConditional deletionProgenitorsPLZFInnate lymphoid cellsExpressionLymphoid tissue inducer cellsLymphoid cellsLTi cellsCellsGATA3FateTranscription factor RORγtILC subsetsLineagesTranscriptionId2DeletionHigh amountsIFN-mediated negative feedback supports bacteria class-specific macrophage inflammatory responses
Gottschalk R, Dorrington M, Dutta B, Krauss K, Martins A, Uderhardt S, Chan W, Tsang J, Torabi-Parizi P, Fraser I, Germain R. IFN-mediated negative feedback supports bacteria class-specific macrophage inflammatory responses. ELife 2019, 8: e46836. PMID: 31385572, PMCID: PMC6684266, DOI: 10.7554/elife.46836.Peer-Reviewed Original ResearchConceptsContext-dependent regulationGram-positive speciesGram-negative bacteriaClass-specific mannerInflammatory responseRegulatory eventsMolecular mechanismsMacrophage inflammatory responseMouse macrophagesLigand pairsInnate immunityInflammatory cytokine productionMacrophage responseBacteriaRegulationSpecific pathogensIL-10Cytokine productionLung infectionProduction dynamicsInhibitory eventsSpeciesMacrophagesNegative feedbackInflammation dynamicsResident Macrophages Cloak Tissue Microlesions to Prevent Neutrophil-Driven Inflammatory Damage
Uderhardt S, Martins A, Tsang J, Lämmermann T, Germain R. Resident Macrophages Cloak Tissue Microlesions to Prevent Neutrophil-Driven Inflammatory Damage. Cell 2019, 177: 541-555.e17. PMID: 30955887, PMCID: PMC6474841, DOI: 10.1016/j.cell.2019.02.028.Peer-Reviewed Original ResearchConceptsTissue-resident macrophagesTissue homeostasisDiverse tissuesCell deathOrgan architectureIndividual cellsNeutrophil swarmsResident macrophagesDense swarmsLocal cell injuryIntravital imagingLocal disruptionParenchymal cell deathDynamic intravital imagingInescapable consequenceCell damageCell injuryHomeostasisMacrophagesCascadeInflammatory damageDamageCellsAccumulationDisruption
2016
Solving Immunology?
Vodovotz Y, Xia A, Read EL, Bassaganya-Riera J, Hafler DA, Sontag E, Wang J, Tsang JS, Day JD, Kleinstein SH, Butte AJ, Altman MC, Hammond R, Sealfon SC. Solving Immunology? Trends In Immunology 2016, 38: 116-127. PMID: 27986392, PMCID: PMC5695553, DOI: 10.1016/j.it.2016.11.006.Peer-Reviewed Original ResearchExpanding the Immunology Toolbox: Embracing Public-Data Reuse and Crowdsourcing
Sparks R, Lau W, Tsang J. Expanding the Immunology Toolbox: Embracing Public-Data Reuse and Crowdsourcing. Immunity 2016, 45: 1191-1204. PMID: 28002728, DOI: 10.1016/j.immuni.2016.12.008.Peer-Reviewed Original ResearchDistinct NF-κB and MAPK Activation Thresholds Uncouple Steady-State Microbe Sensing from Anti-pathogen Inflammatory Responses
Gottschalk R, Martins A, Angermann B, Dutta B, Ng C, Uderhardt S, Tsang J, Fraser I, Meier-Schellersheim M, Germain R. Distinct NF-κB and MAPK Activation Thresholds Uncouple Steady-State Microbe Sensing from Anti-pathogen Inflammatory Responses. Cell Systems 2016, 2: 378-390. PMID: 27237739, PMCID: PMC4919147, DOI: 10.1016/j.cels.2016.04.016.Peer-Reviewed Original ResearchConceptsNF-κBMAPK activationInflammatory mediator productionSet of genesInnate immune response systemNF-κB signalingInnate immune systemSwitch-like mannerMacrophage functional responsesImmune response systemInflammatory mediatorsTLR4 ligandMediator productionInflammatory responseMicrobial stimuliInnate responseImmune systemMAPK signalingMacrophage primingLigand sensitivityHuman macrophagesInverse correlationInvasive pathogensSingle receptorGenesHumoral Fingerprinting of Immune Responses: ‘Super-Resolution’, High-Dimensional Serology
Lau W, Tsang J. Humoral Fingerprinting of Immune Responses: ‘Super-Resolution’, High-Dimensional Serology. Trends In Immunology 2016, 37: 167-169. PMID: 26830541, PMCID: PMC4955921, DOI: 10.1016/j.it.2016.01.003.Peer-Reviewed Original Research
2015
MicroRNA‐455 regulates brown adipogenesis via a novel HIF1an‐AMPK‐PGC1α signaling network
Zhang H, Guan M, Townsend K, Huang T, An D, Yan X, Xue R, Schulz T, Winnay J, Mori M, Hirshman M, Kristiansen K, Tsang J, White A, Cypess A, Goodyear L, Tseng Y. MicroRNA‐455 regulates brown adipogenesis via a novel HIF1an‐AMPK‐PGC1α signaling network. EMBO Reports 2015, 16: 1378-1393. PMID: 26303948, PMCID: PMC4766451, DOI: 10.15252/embr.201540837.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytes, BrownAdipogenesisAdipose Tissue, WhiteAMP-Activated Protein KinasesAnimalsCell DifferentiationCells, CulturedCold TemperatureHumansMiceMice, TransgenicMicroRNAsMixed Function OxygenasesNerve Tissue ProteinsNuclear ProteinsOrganelle BiogenesisPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaRepressor ProteinsSignal TransductionThermogenesisTranscription FactorsConceptsBrown adipose tissueBrown adipogenesisMiR-455Potential therapeutic targetSubcutaneous white fatTransgenic mice displayBrown adipocyte differentiationMRNA microarray profilingHuman metabolic disordersMicroRNA-455Metabolic disordersWhite fatTherapeutic targetAdipose tissueMice displayCold exposureAdipocyte differentiationAdipogenic differentiationAdipogenic programMicroarray profilingAdipogenesisMitochondrial biogenesisFunction studiesKey regulatorNew regulatorLineage relationship of CD8+ T cell subsets is revealed by progressive changes in the epigenetic landscape
Crompton J, Narayanan M, Cuddapah S, Roychoudhuri R, Ji Y, Yang W, Patel S, Sukumar M, Palmer D, Peng W, Wang E, Marincola F, Klebanoff C, Zhao K, Tsang J, Gattinoni L, Restifo N. Lineage relationship of CD8+ T cell subsets is revealed by progressive changes in the epigenetic landscape. Cellular & Molecular Immunology 2015, 13: 502-513. PMID: 25914936, PMCID: PMC4947817, DOI: 10.1038/cmi.2015.32.Peer-Reviewed Original ResearchConceptsHistone modificationsDynamic gene expression programsHistone H3 lysine 4Global gene expression profilingChIP-seq approachH3 lysine 4Gene expression programsT cell differentiationActivation of genesStem cellsGene expression profilingT cell metabolismEpigenetic landscapeLysine 4Expression programsGene expression signaturesEpigenetic mechanismsExpression profilingGene expressionLineage relationshipsCell differentiationT cell ontogenyGenomic landscapeMemory stem cellsExpression signatures