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 ResearchConceptsGlucose toleranceT cellsSystemic metabolismGenome ProjectWild-type T cellsMicroarray analysisCell differentiationNovel roleRhebMammalian targetInsulin receptorT cell differentiationReduced glucose toleranceMarked increaseStrains of miceBeige fatExpressionInsulin sensitivityOverexpressionSystemic overexpressionMetabolismCellsMiceToleranceFurther studies
2022
Cutting Edge: mTORC2 Regulates CD8+ Effector and Memory T Cell Differentiation through Serum and Glucocorticoid Kinase 1.
Patel C, Heikamp E, Xu W, Sun I, Oh M, Sun I, Wen J, Tam A, Blosser R, Powell J. Cutting Edge: mTORC2 Regulates CD8+ Effector and Memory T Cell Differentiation through Serum and Glucocorticoid Kinase 1. The Journal Of Immunology 2022, 209: 2287-2291. PMID: 36469844, PMCID: PMC10065985, DOI: 10.4049/jimmunol.2100669.Peer-Reviewed Original ResearchConceptsT cell differentiationT cellsMemory T cell differentiationMemory precursor phenotypeMemory T cellsEfficacy of vaccinesGlucocorticoid-regulated kinase 1Mechanistic targetRapamycin complex 2 (mTORC2) signalingT cell metabolismT cells resultsKinase 1Memory CD8Acute infectionGlucocorticoid kinase 1Tumor immunotherapyCD8Cell differentiationPrecursor phenotypeNuclear translocationPowerful targetSerumRecall capacityEssential regulatorCell metabolism
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
2020
Targeting glutamine metabolism enhances tumor specific immunity by modulating suppressive myeloid cells
Oh M, Sun I, Zhao L, Leone R, Sun I, Xu W, Collins S, Tam A, Blosser R, Patel C, Englert J, Arwood M, Wen J, Chan-Li Y, Tenora L, Majer P, Rais R, Slusher B, Horton M, Powell J. Targeting glutamine metabolism enhances tumor specific immunity by modulating suppressive myeloid cells. Journal Of Clinical Investigation 2020, 130: 3865-3884. PMID: 32324593, PMCID: PMC7324212, DOI: 10.1172/jci131859.Peer-Reviewed Original ResearchConceptsMyeloid-derived suppressor cellsTumor-associated macrophagesRecruitment of MDSCsGlutamine metabolismMyeloid cellsTumor growthTumor microenvironmentSuppressive myeloid cellsSuppressive immune cellsTumor-specific immunityMyeloid-derived cellsActivation-induced cell deathDevelopment of metastasesImmunogenic cell deathCell deathAntitumor immunityKynurenine levelsSuppressor cellsIDO expressionSpecific immunityImmune cellsTumor glutamine metabolismImmune evasionInflammatory macrophagesSmall molecule inhibitors
2018
mTOR Complex 1 Signaling Regulates the Generation and Function of Central and Effector Foxp3+ Regulatory T Cells
Sun I, Oh M, Zhao L, Patel C, Arwood M, Xu W, Tam A, Blosser R, Wen J, Powell J. mTOR Complex 1 Signaling Regulates the Generation and Function of Central and Effector Foxp3+ Regulatory T Cells. The Journal Of Immunology 2018, 201: 481-492. PMID: 29884702, PMCID: PMC6089237, DOI: 10.4049/jimmunol.1701477.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD8-Positive T-LymphocytesCell DifferentiationFemaleForkhead Transcription FactorsImmunologic MemoryInducible T-Cell Co-Stimulator ProteinLymphocyte ActivationMaleMechanistic Target of Rapamycin Complex 1MiceProgrammed Cell Death 1 ReceptorRegulatory-Associated Protein of mTORSignal TransductionT-Lymphocytes, RegulatoryConceptsT cell activationT cellsCentral TregsGenetic deletionCell activationRegulatory T cell differentiationGeneration of TregsRegulatory T cellsEffector T cellsMemory-like phenotypeT cell differentiationInhibition of mTORSpare respiratory capacityEffector TregsRole of mTORPD-1Treg functionImmune microenvironmentMemory TregsTregsPharmacologic inhibitionDecreased expressionMammalian targetPharmacologic inhibitorsMTOR activityInhibition 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
mTORC2 Signaling Selectively Regulates the Generation and Function of Tissue-Resident Peritoneal Macrophages
Oh M, Collins S, Sun I, Tam A, Patel C, Arwood M, Chan-Li Y, Powell J, Horton M. mTORC2 Signaling Selectively Regulates the Generation and Function of Tissue-Resident Peritoneal Macrophages. Cell Reports 2017, 20: 2439-2454. PMID: 28877476, PMCID: PMC5659290, DOI: 10.1016/j.celrep.2017.08.046.Peer-Reviewed Original ResearchConceptsTissue-resident macrophagesMetabolic reprogrammingTissue-specific cuesUnique differentiation programCritical roleDifferentiation programmingPeritoneal resident macrophagesDifferentiation programMTORC2 activationGATA6 expressionPeritoneal macrophagesResident peritoneal macrophagesTissue microenvironmentHomeostatic functionsReprogrammingSelective roleMacrophage generationMacrophage proliferationDifferentiationDependent fashionResident macrophagesMacrophagesM2 macrophagesGATA6MicroenvironmentExpression 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
Deletion of mTORC1 Activity in CD4+ T Cells Is Associated with Lung Fibrosis and Increased γδ T Cells
Vigeland C, Collins S, Chan-Li Y, Hughes A, Oh M, Powell J, Horton M. Deletion of mTORC1 Activity in CD4+ T Cells Is Associated with Lung Fibrosis and Increased γδ T Cells. PLOS ONE 2016, 11: e0163288. PMID: 27649073, PMCID: PMC5029914, DOI: 10.1371/journal.pone.0163288.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBleomycinCD4-Positive T-LymphocytesDisease Models, AnimalInterleukin-17MacrophagesMechanistic Target of Rapamycin Complex 1MiceMice, KnockoutMultiprotein ComplexesNeutrophilsPulmonary FibrosisReceptors, Antigen, T-Cell, gamma-deltaSignal TransductionT-Lymphocyte SubsetsTOR Serine-Threonine KinasesConceptsΓδ T cellsTh17 cellsDevelopment of fibrosisT cellsPulmonary fibrosisIL-17AChronic inflammationCytokines IL-17ADevelopment of bleomycinNovel therapeutic targetLung dysfunctionLung neutrophilsProgressive fibrosisLung fibrosisM2 macrophagesTherapeutic targetFibrosisIncurable diseaseInflammationMortalityBleomycinCellsILCritical rolePrior studiesAsymmetric 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
The 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 1SHP-1 Regulation of Mast Cell Function in Allergic Inflammation and Anaphylaxis
Zhou L, Oh SY, Zhou Y, Yuan B, Wu F, Oh MH, Wang Y, Takemoto C, Van Rooijen N, Zheng T, Zhu Z. SHP-1 Regulation of Mast Cell Function in Allergic Inflammation and Anaphylaxis. PLOS ONE 2013, 8: e55763. PMID: 23390550, PMCID: PMC3563592, DOI: 10.1371/journal.pone.0055763.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAllergensAnaphylaxisAnimalsBasophilsCell DifferentiationCells, CulturedCytokinesGene ExpressionInflammationInjections, IntravenousLipopolysaccharidesLungMast CellsMiceMice, KnockoutOvalbuminProtein Tyrosine Phosphatase, Non-Receptor Type 6Respiratory HypersensitivitySignal TransductionTh2 CellsConceptsTh2 immune responseAllergic inflammationAirway inflammationMast cell functionImmune responseMast cellsDeficient bone marrow cellsMast cell-deficient miceCell-deficient miceCell functionSevere allergic reactionsWild-type miceSHP-1Bone marrow cellsAirway stimulationAdoptive transferSystemic anaphylaxisAnaphylactic responseClinical symptomsImmunological homeostasisDeficient miceAllergic reactionsType miceAnaphylaxisInflammation
2012
Epicutaneous Exposure to Staphylococcal Superantigen Enterotoxin B Enhances Allergic Lung Inflammation via an IL-17A Dependent Mechanism
Yu J, Oh MH, Park JU, Myers AC, Dong C, Zhu Z, Zheng T. Epicutaneous Exposure to Staphylococcal Superantigen Enterotoxin B Enhances Allergic Lung Inflammation via an IL-17A Dependent Mechanism. PLOS ONE 2012, 7: e39032. PMID: 22848348, PMCID: PMC3407176, DOI: 10.1371/journal.pone.0039032.Peer-Reviewed Original ResearchConceptsIL-17A-dependent mechanismsAtopic dermatitisAirway hyperresponsivenessAtopic marchLung inflammationDependent mechanismDevelopment of ADSeverity of ADEnterotoxin BSystemic Th2 responseAllergic lung inflammationTh17/ILSkin barrier abnormalitiesIL-6 productionSkin of patientsEpicutaneous exposureAllergic rhinitisIL-17ATh2 responsesEpicutaneous sensitizationLymph nodesImmune environmentLesional skinAllergen ovalbuminStimulating lymphocytes
2011
The Role of TSLP in IL-13-Induced Atopic March
Zhu Z, Oh MH, Yu J, Liu YJ, Zheng T. The Role of TSLP in IL-13-Induced Atopic March. Scientific Reports 2011, 1: 23. PMID: 22355542, PMCID: PMC3251897, DOI: 10.1038/srep00023.Peer-Reviewed Original ResearchConceptsThymic stromal lymphopoietinAtopic dermatitisAtopic marchAirway hyperresponsivenessLevels of TSLPRole of TSLPIL-13 transgenic miceAcute atopic dermatitisAllergic asthma responsesChronic atopic dermatitisHuman atopic dermatitisImmune cell productionSkin of miceSystemic Th2 immunityAD skinAsthma responseLung inflammationMucus hypersecretionTh2 immunitySerum IgE.Th2 cytokinesIL-13AD phenotypeTransgenic miceDependent mechanismIL-13 Induces Skin Fibrosis in Atopic Dermatitis by Thymic Stromal Lymphopoietin
Oh MH, Oh SY, Yu J, Myers AC, Leonard WJ, Liu YJ, Zhu Z, Zheng T. IL-13 Induces Skin Fibrosis in Atopic Dermatitis by Thymic Stromal Lymphopoietin. The Journal Of Immunology 2011, 186: 7232-7242. PMID: 21576506, PMCID: PMC3399513, DOI: 10.4049/jimmunol.1100504.Peer-Reviewed Original ResearchConceptsThymic stromal lymphopoietinRole of TSLPAtopic dermatitisSkin fibrosisTSLP receptorIL-13Fibrotic remodelingNeutralization of TSLPIL-13 transgenic miceAD skin lesionsElevated IL-13AD-like phenotypeHuman atopic dermatitisReduction of fibrosisNumber of fibrocytesReduced skin inflammationFibrocyte functionTh2 responsesAD lesionsSkin inflammationAD patientsSkin lesionsFurther progressionTissue fibrosisTransgenic mice
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 mice