2023
Serendipitous Discovery of T Cell–Produced KLK1b22 as a Regulator of Systemic Metabolism
Arwood M, Sun I, Patel C, Sun I, Oh M, Bettencourt I, Claiborne M, Chan-Li Y, Zhao L, Waickman A, Mavrothalassitis O, Wen J, Aja S, Powell J. Serendipitous Discovery of T Cell–Produced KLK1b22 as a Regulator of Systemic Metabolism. ImmunoHorizons 2023, 7: 493-507. PMID: 37358498, PMCID: PMC10580127, DOI: 10.4049/immunohorizons.2300016.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytes, BeigeAnimalsBlood GlucoseFemaleInsulin ResistanceKallikreinsMaleMiceMice, Inbred C57BLT-LymphocytesConceptsGlucose toleranceT cellsSystemic metabolismGenome ProjectWild-type T cellsMicroarray analysisCell differentiationNovel roleRhebMammalian targetInsulin receptorT cell differentiationReduced glucose toleranceMarked increaseStrains of miceBeige fatExpressionInsulin sensitivityOverexpressionSystemic overexpressionMetabolismCellsMiceToleranceFurther studies
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 metabolismSignaling
2019
Glutamine blockade induces divergent metabolic programs to overcome tumor immune evasion
Leone R, Zhao L, Englert J, Sun I, Oh M, Sun I, Arwood M, Bettencourt I, Patel C, Wen J, Tam A, Blosser R, Prchalova E, Alt J, Rais R, Slusher B, Powell J. Glutamine blockade induces divergent metabolic programs to overcome tumor immune evasion. Science 2019, 366: 1013-1021. PMID: 31699883, PMCID: PMC7023461, DOI: 10.1126/science.aav2588.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAzo CompoundsCaproatesCD8-Positive T-LymphocytesCitric Acid CycleEnergy MetabolismFemaleGlucoseGlutamineImmunologic MemoryImmunotherapy, AdoptiveLymphocyte ActivationLymphocytes, Tumor-InfiltratingMaleMice, Inbred BALB CMice, Inbred C57BLNeoplasms, ExperimentalTumor EscapeTumor MicroenvironmentConceptsEffector T cellsT cellsTumor immune evasionCancer cellsPotent antitumor responsesImmune cell functionAntitumor responseImmunosuppressive microenvironmentTumor immunotherapyCancer immunotherapyMice suppressesImmune evasionCell functionOxidative metabolismGlycolytic metabolismGlutamine antagonistImmunotherapyMetabolic characteristicsMetabolic programsTumorsMetabolic checkpointDivergent changesMetabolismCellsAntagonism
2018
Inhibition of the adenosine A2a receptor modulates expression of T cell coinhibitory receptors and improves effector function for enhanced checkpoint blockade and ACT in murine cancer models
Leone R, Sun I, Oh M, Sun I, Wen J, Englert J, Powell J. Inhibition of the adenosine A2a receptor modulates expression of T cell coinhibitory receptors and improves effector function for enhanced checkpoint blockade and ACT in murine cancer models. Cancer Immunology, Immunotherapy 2018, 67: 1271-1284. PMID: 29923026, PMCID: PMC11028354, DOI: 10.1007/s00262-018-2186-0.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine A2 Receptor AntagonistsAnimalsAntigens, CDCD8-Positive T-LymphocytesColonic NeoplasmsFemaleGene Expression Regulation, NeoplasticImmunotherapyLymphocyte Activation Gene 3 ProteinLymphocytes, Tumor-InfiltratingMaleMelanoma, ExperimentalMiceMice, Inbred BALB CMice, Inbred C57BLProgrammed Cell Death 1 ReceptorReceptor, Adenosine A2AReceptors, Antigen, T-CellT-Lymphocytes, RegulatoryTumor Cells, CulturedTumor MicroenvironmentXenograft Model Antitumor AssaysConceptsA2AR blockadePD-1T cellsImmune responseA2A receptorsCD39/CD73 axisTumor immune evasionEffector T cellsLAG-3 expressionRegulatory T cellsT cell persistenceTumor bearing miceAdenosine A2A receptorsMurine cancer modelsCoinhibitory receptorsCheckpoint blockadeCheckpoint therapyRegulatory cellsLymph nodesImmunologic responseImmunotherapy regimensInflammatory milieuPharmacologic blockadeA2AR antagonistAdenosine levels
2017
Expression of IL-22 in the Skin Causes Th2-Biased Immunity, Epidermal Barrier Dysfunction, and Pruritus via Stimulating Epithelial Th2 Cytokines and the GRP Pathway
Lou H, Lu J, Choi EB, Oh MH, Jeong M, Barmettler S, Zhu Z, Zheng T. Expression of IL-22 in the Skin Causes Th2-Biased Immunity, Epidermal Barrier Dysfunction, and Pruritus via Stimulating Epithelial Th2 Cytokines and the GRP Pathway. The Journal Of Immunology 2017, 198: 2543-2555. PMID: 28228560, PMCID: PMC5360537, DOI: 10.4049/jimmunol.1600126.Peer-Reviewed Original ResearchConceptsGastrin-releasing peptideType 2 cytokinesAtopic dermatitisIL-22GRP receptorAD skinDevelopment of ADPathogenesis of ADExpression of GRPHouse dust mite allergenDermal immune cellsIntensity of pruritusAD-like phenotypeThymic stromal lymphopoietinCytokine IL-22Human atopic dermatitisSystemic immune responsesEpidermal barrier dysfunctionImportant pathogenic roleTh2-biased immunitySkin of patientsDust mite allergenSkin of miceChronic pruritic dermatitisAllergen exposure
2016
Asymmetric inheritance of mTORC1 kinase activity during division dictates CD8+ T cell differentiation
Pollizzi K, Sun I, Patel C, Lo Y, Oh M, Waickman A, Tam A, Blosser R, Wen J, Delgoffe G, Powell J. Asymmetric inheritance of mTORC1 kinase activity during division dictates CD8+ T cell differentiation. Nature Immunology 2016, 17: 704-711. PMID: 27064374, PMCID: PMC4873361, DOI: 10.1038/ni.3438.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD8-Positive T-LymphocytesCell DifferentiationCell DivisionCell SurvivalCells, CulturedFemaleGlycolysisImmunologic MemoryLipid MetabolismLysosomesMaleMechanistic Target of Rapamycin Complex 1MiceMice, Inbred C57BLMice, TransgenicMultiprotein ComplexesPrecursor Cells, T-LymphoidProtein TransportReceptors, Antigen, T-CellSignal TransductionTOR Serine-Threonine Kinases
2015
mTORC1 and mTORC2 selectively regulate CD8+ T cell differentiation
Pollizzi K, Patel C, Sun I, Oh M, Waickman A, Wen J, Delgoffe G, Powell J. mTORC1 and mTORC2 selectively regulate CD8+ T cell differentiation. Journal Of Clinical Investigation 2015, 125: 2090-2108. PMID: 25893604, PMCID: PMC4463194, DOI: 10.1172/jci77746.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsCarrier ProteinsCD4-CD8 RatioCD8-Positive T-LymphocytesCell Line, TumorDeoxyglucoseFemaleGenes, ReporterGlycolysisImmunologic MemoryInterferon-gammaLymphocyte ActivationLymphopoiesisMaleMechanistic Target of Rapamycin Complex 1Mechanistic Target of Rapamycin Complex 2Melanoma, ExperimentalMiceMice, CongenicMice, Inbred C57BLMonomeric GTP-Binding ProteinsMultiprotein ComplexesNeuropeptidesOvalbuminPeptide FragmentsPhosphorylationProtein Processing, Post-TranslationalProto-Oncogene Proteins c-aktRapamycin-Insensitive Companion of mTOR ProteinRas Homolog Enriched in Brain ProteinRecombinant Fusion ProteinsSirolimusThymomaTOR Serine-Threonine KinasesTransduction, GeneticTumor Necrosis Factor-alphaConceptsGeneration of CD8T cell effectorsT cellsTuberous sclerosis complex 2Cell effectorsT cell effector responsesMemory-like T cellsEffector cell subsetsT cell memoryDifferentiation of CD4T cell-specific deletionT cell differentiationCell-specific deletionSurface marker expressionMTOR-dependent pathwayEvaluation of miceEffector CD8Antitumor immunityEffector phenotypeEffector cellsCell subsetsRecall responsesVaccine efficacyEffector responsesCD8
2014
Regulation of Nasal Airway Homeostasis and Inflammation in Mice by SHP-1 and Th2/Th1 Signaling Pathways
Cho SH, Oh SY, Lane AP, Lee J, Oh MH, Lee S, Zheng T, Zhu Z. Regulation of Nasal Airway Homeostasis and Inflammation in Mice by SHP-1 and Th2/Th1 Signaling Pathways. PLOS ONE 2014, 9: e103685. PMID: 25090641, PMCID: PMC4121172, DOI: 10.1371/journal.pone.0103685.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChemokinesEosinophiliaGelatinHomeostasisInflammationInterferon-gammaMatrix Metalloproteinase 2Matrix Metalloproteinase 9MetaplasiaMice, Inbred C57BLMice, Mutant StrainsMucusNasal Lavage FluidNasal MucosaProtein Tyrosine Phosphatase, Non-Receptor Type 6RhinitisSignal TransductionTh1 CellsTh2 CellsConceptsMatrix metalloproteinasesNasal inflammationAllergic rhinitisTh1 cytokinesInflammatory cellsTh2 cytokinesNasal airwayChronic inflammatory diseaseExpression of cytokinesTh2-skewed inflammationIFN-γ geneMucus metaplasiaTh1 paradigmAirway homeostasisInflammatory mediatorsTh2 lymphocytesImmune homeostasisInflammatory diseasesViable motheaten miceInflammationTransepithelial migrationCytokinesMev miceClearance mechanismsTh2The AGC kinase SGK1 regulates TH1 and TH2 differentiation downstream of the mTORC2 complex
Heikamp E, Patel C, Collins S, Waickman A, Oh M, Sun I, Illei P, Sharma A, Naray-Fejes-Toth A, Fejes-Toth G, Misra-Sen J, Horton M, Powell J. The AGC kinase SGK1 regulates TH1 and TH2 differentiation downstream of the mTORC2 complex. Nature Immunology 2014, 15: 457-464. PMID: 24705297, PMCID: PMC4267697, DOI: 10.1038/ni.2867.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAnimalsAsthmaCell DifferentiationCells, CulturedEndosomal Sorting Complexes Required for TransportGene Expression RegulationHepatocyte Nuclear Factor 1-alphaImmediate-Early ProteinsInterferon-gammaMechanistic Target of Rapamycin Complex 2Melanoma, ExperimentalMiceMice, Inbred C57BLMice, KnockoutMultiprotein ComplexesNedd4 Ubiquitin Protein LigasesPoxviridae InfectionsProtein Serine-Threonine KinasesT Cell Transcription Factor 1Th1 CellsTh2 CellsTOR Serine-Threonine KinasesTranscription FactorsTumor BurdenUbiquitin-Protein LigasesVaccinia virus
2013
TRPA1-Dependent Pruritus in IL-13–Induced Chronic Atopic Dermatitis
Oh MH, Oh SY, Lu J, Lou H, Myers AC, Zhu Z, Zheng T. TRPA1-Dependent Pruritus in IL-13–Induced Chronic Atopic Dermatitis. The Journal Of Immunology 2013, 191: 5371-5382. PMID: 24140646, PMCID: PMC4175413, DOI: 10.4049/jimmunol.1300300.Peer-Reviewed Original ResearchMeSH KeywordsAcetanilidesAnimalsCalcium ChannelsCells, CulturedChronic DiseaseCytokinesDermatitis, AtopicDisease Models, AnimalHumansInterleukin-13Mast CellsMiceMice, Inbred C57BLMice, TransgenicNerve FibersNerve Tissue ProteinsNeuropeptidesPruritusPurinesTh1-Th2 BalanceTransient Receptor Potential ChannelsTRPA1 Cation ChannelUp-RegulationConceptsTransient receptor potential ankyrin 1Chronic atopic dermatitisAtopic dermatitisMast cellsChronic itchTRPA1 expressionAfferent nervesIL-13Nerve fibersInhibition of TRPA1Histamine-independent itchSensory nerve fibersAfferent nerve fibersDorsal root gangliaNovel neural mechanismAD skinAD miceItch pathwaysLesional skinRoot gangliaInflammatory environmentHealthy subjectsSpecific antagonistMouse modelAnkyrin 1
2009
SHP-1 Deficient Mast Cells Are Hyperresponsive to Stimulation and Critical in Initiating Allergic Inflammation in the Lung
Zhang L, Oh SY, Wu X, Oh MH, Wu F, Schroeder JT, Takemoto CM, Zheng T, Zhu Z. SHP-1 Deficient Mast Cells Are Hyperresponsive to Stimulation and Critical in Initiating Allergic Inflammation in the Lung. The Journal Of Immunology 2009, 184: 1180-1190. PMID: 20042576, PMCID: PMC4755278, DOI: 10.4049/jimmunol.0901972.Peer-Reviewed Original ResearchConceptsBone marrow-derived mast cellsAllergic asthma phenotypeMarrow-derived mast cellsMast cellsTh2 cytokinesMev miceAsthma phenotypesTh2 cytokines IL-4Allergic inflammatory responseTh2 cytokine productionRelease of mediatorsCytokines IL-4Mast cell productionT cells 2SHP-1 deficiencySrc homology region 2 domain-containing phosphatase-1Amount of mediatorMast cell developmentPulmonary inflammationAllergic inflammationCytokine productionTh2 phenotypeIL-13IL-4Deficient mast cells
2008
Transgenic Expression of Interleukin-13 in the Skin Induces a Pruritic Dermatitis and Skin Remodeling
Zheng T, Oh MH, Oh SY, Schroeder JT, Glick AB, Zhu Z. Transgenic Expression of Interleukin-13 in the Skin Induces a Pruritic Dermatitis and Skin Remodeling. Journal Of Investigative Dermatology 2008, 129: 742-751. PMID: 18830273, PMCID: PMC4356214, DOI: 10.1038/jid.2008.295.Peer-Reviewed Original ResearchConceptsAtopic dermatitisIL-13Transgenic modelElevated serum total IgEPathogenesis of ADPeripheral blood mononuclear cellsPruritic eczematous lesionsSerum total IgEThymic stromal lymphopoietinSystemic immune responsesUpregulation of chemokinesBlood mononuclear cellsKeratin 5 promoterChronic inflammatory phenotypeEczematous lesionsInducible transgenic modelDermal infiltrationTotal IgEAllergic diseasesClinical manifestationsDermal inflammationInflammatory phenotypeMononuclear cellsIL-4Langerhans cells
2007
TH2 and TH1 lung inflammation induced by airway allergen sensitization with low and high doses of double-stranded RNA
Jeon SG, Oh SY, Park HK, Kim YS, Shim EJ, Lee HS, Oh MH, Bang B, Chun EY, Kim SH, Gho YS, Zhu Z, Kim YY, Kim YK. TH2 and TH1 lung inflammation induced by airway allergen sensitization with low and high doses of double-stranded RNA. Journal Of Allergy And Clinical Immunology 2007, 120: 803-812. PMID: 17610940, DOI: 10.1016/j.jaci.2007.05.030.Peer-Reviewed Original ResearchConceptsRespiratory viral infectionsAllergen sensitizationLung inflammationViral infectionAirway sensitizationIL-4Immune responseMouse modelHigh dosesIL-13-deficient miceIFN-gamma-deficient miceT-bet-deficient miceToll-like receptor 3Airway allergen exposureAllergic lung inflammationAdaptive immune responsesToll-like receptorsIL-4 expressionSTAT6-deficient miceNovel mouse modelIFN-gamma expressionAllergen exposurePathophysiologic mechanismsIL-13Deficient miceAirway Exposure Levels of Lipopolysaccharide Determine Type 1 versus Type 2 Experimental Asthma
Kim YK, Oh SY, Jeon SG, Park HW, Lee SY, Chun EY, Bang B, Lee HS, Oh MH, Kim YS, Kim JH, Gho YS, Cho SH, Min KU, Kim YY, Zhu Z. Airway Exposure Levels of Lipopolysaccharide Determine Type 1 versus Type 2 Experimental Asthma. The Journal Of Immunology 2007, 178: 5375-5382. PMID: 17404323, DOI: 10.4049/jimmunol.178.8.5375.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnimalsAsthmaBronchial HyperreactivityFemaleHumansInterferon-gammaInterleukin-12LipopolysaccharidesMaleMiceMice, Inbred BALB CMice, Inbred C57BLMiddle AgedOvalbuminReceptors, Tumor Necrosis FactorRNA, MessengerSignal TransductionSTAT4 Transcription FactorTh1 CellsTh2 CellsTransforming Growth Factor beta1Tumor Necrosis Factor-alphaConceptsHigh-dose LPSLow-dose LPSAsthma phenotypesAdaptive immune responsesImmune responseAirway hyperresponsivenessAllergen sensitizationTNF-alpha receptor-deficient miceType 1IFN-gamma-deficient miceSevere asthma patientsReceptor-deficient miceAllergen-specific IgEExposure levelsIL-12 expressionTNF-alpha expressionIFN-gamma expressionLow LPS levelsNoneosinophilic inflammationAirway inflammationAllergic asthmaNeutrophilic inflammationSevere asthmaAirway exposureAsthma patientsRecombinant basic fibroblast growth factor inhibits the airway hyperresponsiveness, mucus production, and lung inflammation induced by an allergen challenge
Jeon SG, Lee CG, Oh MH, Chun EY, Gho YS, Cho SH, Kim JH, Min KU, Kim YY, Kim YK, Elias JA. Recombinant basic fibroblast growth factor inhibits the airway hyperresponsiveness, mucus production, and lung inflammation induced by an allergen challenge. Journal Of Allergy And Clinical Immunology 2007, 119: 831-837. PMID: 17289133, DOI: 10.1016/j.jaci.2006.12.653.Peer-Reviewed Original ResearchConceptsAsthma mouse modelLung inflammationBasic fibroblast growth factorAsthma phenotypesMucus productionFibroblast growth factorAllergen challengeTg miceRecombinant FGF2Therapeutic effectMouse modelWild-type control miceGrowth factorDevelopment of AHRTGF-beta1 miceRegional lymph nodesWhole-body plethysmographyDevelopment of asthmaBronchoalveolar lavage cellularityRecombinant basic fibroblast growth factorFGF2-deficient micePeriodic acid-Schiff stainingFGF2 mRNA expressionRole of FGF2Acid-Schiff staining