2024
IL-1 receptor 1 signaling shapes the development of viral antigen-specific CD4+ T cell responses following COVID-19 mRNA vaccination
Park H, Shin M, Shin J, Kim H, Kang B, Par-Young J, Unlu S, Afinogenova Y, Catanzaro J, Young J, Kim M, Lee S, Jeon S, You S, Racke M, Bucala R, Kang I. IL-1 receptor 1 signaling shapes the development of viral antigen-specific CD4+ T cell responses following COVID-19 mRNA vaccination. EBioMedicine 2024, 103: 105114. PMID: 38640835, PMCID: PMC11041015, DOI: 10.1016/j.ebiom.2024.105114.Peer-Reviewed Original ResearchConceptsCD4<sup>+</sup> T cellsCOVID-19 mRNA vaccinesAntigen-specific CD4<sup>+</sup> T cell responsesT cell responsesPrimary antibody deficiencyCD4<sup>+</sup> T cell responsesT cellsIL-1R1MRNA vaccinesIL-1IgG antibodiesAntigen-specific CD4<sup>+</sup> T cellsCD4+ T cell responsesLevels of IL-1R1Human CD4<sup>+</sup> T cellsIL-1 receptor 1Healthy individualsDose of COVID-19 mRNA vaccineAntigen-specific CD4IL-1R1 expressionT cell immunityRepetitive antigenic stimulationCytokines interleukin (IL)-1Immune response to virusesExpression of IL-1R1
2023
Aging gene signature of memory CD8+ T cells is associated with neurocognitive functioning in Alzheimer’s disease
Young J, Park H, Kim M, Par-Young J, Bartlett H, Kim H, Unlu S, Osmani L, Shin M, Bucala R, van Dyck C, Allore H, Mecca A, You S, Kang I. Aging gene signature of memory CD8+ T cells is associated with neurocognitive functioning in Alzheimer’s disease. Immunity & Ageing 2023, 20: 71. PMID: 38042785, PMCID: PMC10693128, DOI: 10.1186/s12979-023-00396-y.Peer-Reviewed Original ResearchPeripheral bloodT cellsAlzheimer's diseaseEM CD8Memory CD8Gene signatureAge-related immune changesIL-7 receptor alphaEffector memory CD8Strong risk factorT cell expansionAD genesAge-associated expansionImmune changesRisk factorsCD8Dementia patientsIL-7RNeuropsychological testingReceptor alphaNeurocognitive functionRT-qPCR resultsDisease severityPatientsNormal personsVISTA (PD-1H) Is a Crucial Immune Regulator to Limit Pulmonary Fibrosis.
Kim S, Adams T, Hu Q, Shin H, Chae G, Lee S, Sharma L, Kwon H, Lee F, Park H, Huh W, Manning E, Kaminski N, Sauler M, Chen L, Song J, Kim T, Kang M. VISTA (PD-1H) Is a Crucial Immune Regulator to Limit Pulmonary Fibrosis. American Journal Of Respiratory Cell And Molecular Biology 2023, 69: 22-33. PMID: 36450109, PMCID: PMC10324045, DOI: 10.1165/rcmb.2022-0219oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisImmune regulatorsTherapeutic potentialHuman idiopathic pulmonary fibrosisCrucial immune regulatorsNovel immune regulatorPulmonary fibrosis micePulmonary fibrosis modelNovel therapeutic targetRole of VISTAWild-type littermatesMonocyte-derived macrophagesT lymphocyte lineageVISTA expressionIPF treatmentAntibody treatmentImmune landscapeFibrotic mediatorsLung fibrosisFibrosis miceInflammatory responseFibrosis modelMyeloid populationsTherapeutic target
2022
Implication of IL-7 receptor alpha chain expression by CD8+ T cells and its signature in defining biomarkers in aging
Shin M, Park H, Young J, Kang I. Implication of IL-7 receptor alpha chain expression by CD8+ T cells and its signature in defining biomarkers in aging. Immunity & Ageing 2022, 19: 66. PMID: 36544153, PMCID: PMC9768896, DOI: 10.1186/s12979-022-00324-6.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsT cellsImmune agingHost defenseIL-7 receptor alpha chainFrequencies of naïveT cell subsetsAlpha chain expressionAssociation of CD8Age-associated conditionsReceptor alpha chainMemory CD8Treatment of illnessCell subsetsInflammatory disordersIL-7RαCD8High riskImmune functionTherapeutic interventionsImmune systemPotential biomarkersGene signatureChain expressionOlder adultsBiomarkersAlterations in high‐dimensional T‐cell profile and gene signature of immune aging in HIV‐infected older adults without viremia
Shin MS, Park H, Salahuddin S, Montgomery RR, Emu B, Shaw AC, Kang I. Alterations in high‐dimensional T‐cell profile and gene signature of immune aging in HIV‐infected older adults without viremia. Aging Cell 2022, 21: e13702. PMID: 36036630, PMCID: PMC9577958, DOI: 10.1111/acel.13702.Peer-Reviewed Original ResearchConceptsOlder human immunodeficiency virusPeripheral blood mononuclear cellsHuman immunodeficiency virusAntiretroviral therapyT cellsDetectable viremiaMemory CD8HIV infectionAge-associated immune alterationsYoung human immunodeficiency virusReplication-competent HIV-1Combination antiretroviral therapyEffector memory CD8T-cell countsSubset of CD4T cell profileBlood mononuclear cellsAgeing-associated genesEM CD8Immune alterationsMemory CD4Immune agingImmunodeficiency virusInflammatory moleculesMononuclear cellsDefining Clinical and Immunological Predictors of Poor Immune Responses to COVID-19 mRNA Vaccines in Patients with Primary Antibody Deficiency
Shin JJ, Par-Young J, Unlu S, McNamara A, Park HJ, Shin MS, Gee RJ, Doyle H, Afinogenova Y, Zidan E, Kwah J, Russo A, Mamula M, Hsu FI, Catanzaro J, Racke M, Bucala R, Wilen C, Kang I. Defining Clinical and Immunological Predictors of Poor Immune Responses to COVID-19 mRNA Vaccines in Patients with Primary Antibody Deficiency. Journal Of Clinical Immunology 2022, 42: 1137-1150. PMID: 35713752, PMCID: PMC9203263, DOI: 10.1007/s10875-022-01296-4.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, ViralCD8-Positive T-LymphocytesCommon Variable ImmunodeficiencyCOVID-19COVID-19 VaccinesHumansImmunity, CellularImmunoglobulin AImmunoglobulin GMRNA VaccinesPrimary Immunodeficiency DiseasesRNA, MessengerSARS-CoV-2Spike Glycoprotein, CoronavirusVaccinationVaccinesVaccines, SyntheticConceptsCommon variable immune deficiencyT cellsImmune responseIgG responsesCVID patientsMRNA vaccinesB cellsCoronavirus disease 2019 (COVID-19) mRNA vaccinesCOVID-19 mRNA vaccinesBaseline immune profileHistory of autoimmunityPrimary antibody deficiencyT cell responsesCellular immune responsesPoor immune responseVariable immune deficiencyMemory B cellsSARS-CoV-2 spike proteinBaseline IgGCVID diagnosisEM CD8Immunological predictorsPAD cohortSpecific CD4Immune profileAHCC®, a Standardized Extract of Cultured Lentinula Edodes Mycelia, Promotes the Anti-Tumor Effect of Dual Immune Checkpoint Blockade Effect in Murine Colon Cancer
Park HJ, Boo S, Park I, Shin MS, Takahashi T, Takanari J, Homma K, Kang I. AHCC®, a Standardized Extract of Cultured Lentinula Edodes Mycelia, Promotes the Anti-Tumor Effect of Dual Immune Checkpoint Blockade Effect in Murine Colon Cancer. Frontiers In Immunology 2022, 13: 875872. PMID: 35514996, PMCID: PMC9066372, DOI: 10.3389/fimmu.2022.875872.Peer-Reviewed Original ResearchConceptsDual immune checkpoint blockadeImmune checkpoint blockadeAnti-tumor effectsCheckpoint blockadeBearing miceStandardized extractTumor growthMC38 tumor-bearing miceGut microbiomePD-1/CTLATumor-infiltrating CD8Cell functionCancer bearing miceT cell functionKi-67 expressionImmune cell functionMurine colon cancerTumor bearing miceTumor-bearing miceTreatment of cancerTreatment strategiesT cellsTherapeutic effectGranzyme BColon cancerT cell response to influenza vaccination remains intact in adults with congenital heart disease who underwent early thymectomy
Leone DM, Park HJ, Unlu S, Gurvitz M, Kang I, Elder RW. T cell response to influenza vaccination remains intact in adults with congenital heart disease who underwent early thymectomy. International Journal Of Cardiology Congenital Heart Disease 2022, 8: 100359. PMID: 35600131, PMCID: PMC9122016, DOI: 10.1016/j.ijcchd.2022.100359.Peer-Reviewed Original ResearchT cell responsesCongenital heart diseaseT cellsInfluenza vaccinationEarly thymectomyMemory CD4Heart diseaseAdequate T-cell responsesCell responsesT cell distributionT cell subsetsNaïve T cellsCongenital heart surgeryYears of ageHemagglutination inhibition assaysRoutine vaccinationVaccine immunityCell subsetsMean ageHeart surgeryNaïve CD4Healthy controlsThymectomyBlood samplesDiminished response
2021
Nucleotide‐binding domain and leucine‐rich‐repeat‐containing protein X1 deficiency induces nicotinamide adenine dinucleotide decline, mechanistic target of rapamycin activation, and cellular senescence and accelerates aging lung‐like changes
Shin HJ, Kim S, Park H, Shin M, Kang I, Kang M. Nucleotide‐binding domain and leucine‐rich‐repeat‐containing protein X1 deficiency induces nicotinamide adenine dinucleotide decline, mechanistic target of rapamycin activation, and cellular senescence and accelerates aging lung‐like changes. Aging Cell 2021, 20: e13410. PMID: 34087956, PMCID: PMC8282248, DOI: 10.1111/acel.13410.Peer-Reviewed Original ResearchConceptsCellular senescenceActivation of mTORNucleotide-binding domainCellular senescence responseReplicative cellular senescenceNLR family membersOrganismal agingCellular physiologyMitochondrial moleculesSenescence responseCellular locationProtein X1Crucial regulatorMechanistic targetMitochondrial functionMolecular hallmarksNLRX1 functionRapamycin (mTOR) activationMitochondrial dysfunctionSenescenceMTORPharmacological inhibitionNLRX1BiologyAging LungCo-inhibitor expression on tumor infiltrating and splenic lymphocytes after dual checkpoint inhibition in a microsatellite stable model of colorectal cancer
Slovak RJ, Park HJ, Kamp WM, Ludwig JM, Kang I, Kim HS. Co-inhibitor expression on tumor infiltrating and splenic lymphocytes after dual checkpoint inhibition in a microsatellite stable model of colorectal cancer. Scientific Reports 2021, 11: 6956. PMID: 33772035, PMCID: PMC7997991, DOI: 10.1038/s41598-021-85810-5.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDCD4-Positive T-LymphocytesCell Line, TumorCell ProliferationColorectal NeoplasmsCTLA-4 AntigenFemaleHepatitis A Virus Cellular Receptor 2Immune Checkpoint InhibitorsLymphocyte Activation Gene 3 ProteinLymphocytes, Tumor-InfiltratingMaleMiceMice, Inbred BALB CMicrosatellite RepeatsProgrammed Cell Death 1 ReceptorSpleenT-Lymphocytes, CytotoxicConceptsDual checkpoint inhibitionPD-1 inhibitionColorectal cancerCheckpoint inhibitionPD-1Checkpoint inhibitorsT cellsImmune responseRobust anti-tumor immune responseAnti-PD-1 groupAnti-PD-1 antibodyAnti-tumor immune responseMicrosatellite stable colorectal cancerDual PD-1Majority of patientsDeficient mismatch repairStable colorectal cancerCTLA-4 inhibitionTumor growth rateHigh microsatellite instabilityPotential escape mechanismsCombination immunotherapyImmunosuppressive checkpointsTumoral infiltrationDual therapy
2020
IL-7 receptor alpha defines heterogeneity and signature of human effector memory CD8+ T cells in high dimensional analysis
Shin MS, Kim D, Yim K, Park HJ, You S, Dong X, Koumpouras F, Shaw AC, Fan R, Krishnaswamy S, Kang I. IL-7 receptor alpha defines heterogeneity and signature of human effector memory CD8+ T cells in high dimensional analysis. Cellular Immunology 2020, 355: 104155. PMID: 32619811, PMCID: PMC7415611, DOI: 10.1016/j.cellimm.2020.104155.Peer-Reviewed Original ResearchConceptsSingle-cell RNA-seqHuman effector memory CD8Effector memory CD8T cellsIL-7RαMemory CD8Gene regulationTranscription factorsRNA-seqPossible biological significanceDownstream eventsEM CD8Expression patternsExpressional relationshipDifferential expressionCytokine receptorsComprehensive landscapeHigh-dimensional cytometryBiological significanceIL-7 receptor alphaKey moleculesIL-7 receptor alpha chainReceptor alpha chainBiological implicationsHeterogeneous cell subsetsDefining heterogeneity and biological signature in human effector memory CD8+ T cells expressing different levels of IL-7 receptor alpha by high-dimensional analysis
Shin M, Kim D, Park H, Dong X, Koumpouras F, Kang I. Defining heterogeneity and biological signature in human effector memory CD8+ T cells expressing different levels of IL-7 receptor alpha by high-dimensional analysis. The Journal Of Immunology 2020, 204: 154.19-154.19. DOI: 10.4049/jimmunol.204.supp.154.19.Peer-Reviewed Original ResearchHuman effector memory CD8EM CD8Effector memory CD8T cellsIL-7RαMemory CD8Cell subsetsIL-7 receptor alphaIL-7 receptor alpha chainT cell subsetsCo-stimulatory moleculesT cell heterogeneityHigh-dimensional single-cell analysisReceptor alpha chainLupus patientsImmune landscapeCell surface moleculesHeterogeneous cell subsetsT-betCD8Effector functionsDifferential expressionReceptor alphaSingle-cell RNA-seq analysisPathologic conditionsQuantification of immune response after dual checkpoint inhibition in a microsatellite stable model of colorectal cancer.
Kamp W, Park H, Slovak R, Ludwig J, Kang I, Kim H. Quantification of immune response after dual checkpoint inhibition in a microsatellite stable model of colorectal cancer. Journal Of Clinical Oncology 2020, 38: 160-160. DOI: 10.1200/jco.2020.38.4_suppl.160.Peer-Reviewed Original ResearchDual immune checkpoint blockadeAnti-PD-1 antibodyColorectal cancerPD-1T cellsImmune responseMurine colorectal cancer cellsBALB/c miceDual checkpoint inhibitionExpression of TIM3Subcutaneous flank injectionNumber of CD8PD-1 inhibitionImmune checkpoint blockadeDeficient mismatch repairColorectal cancer cellsHigh microsatellite instabilitySignificant clinical impactPotential escape mechanismsCombination immunotherapyImmunosuppressive checkpointsCheckpoint inhibitorsMonotherapy groupCheckpoint blockadeMost patientsSystemic impact on tumor growth after combined immuno-thermal ablation in a murine model of colorectal cancer.
Slovak R, Park H, Kamp W, Ludwig J, Kang I, Kim H. Systemic impact on tumor growth after combined immuno-thermal ablation in a murine model of colorectal cancer. Journal Of Clinical Oncology 2020, 38: 198-198. DOI: 10.1200/jco.2020.38.4_suppl.198.Peer-Reviewed Original ResearchDual immune checkpoint blockadeTreatment days 0Target tumorTumor volumeDay 0Anti-cancer immune responseBALB/c miceAddition of immunotherapyImmune checkpoint blockadeTreatment day 2Colorectal cancer cellsInjection of antibodiesFull ablationCheckpoint blockadeColorectal cancerC miceSham injectionMean changeImmune responseMurine modelControl animalsCryoablationDay 2Tumor growthFlank injection
2019
The Effects of AHCC®, a Standardized Extract of Cultured Lentinura edodes Mycelia, on Natural Killer and T Cells in Health and Disease: Reviews on Human and Animal Studies
Shin MS, Park HJ, Maeda T, Nishioka H, Fujii H, Kang I. The Effects of AHCC®, a Standardized Extract of Cultured Lentinura edodes Mycelia, on Natural Killer and T Cells in Health and Disease: Reviews on Human and Animal Studies. Journal Of Immunology Research 2019, 2019: 3758576. PMID: 31930148, PMCID: PMC6942843, DOI: 10.1155/2019/3758576.Peer-Reviewed Original ResearchConceptsNatural killerEffects of AHCCT cellsStandardized extractImmune systemImmune cellsAnimal studiesClinical implicationsHost defenseAHCCHealth conditionsTraditional medicineMushroom extractsDiseaseExact effectKillerCellsHealthMixture of nutrientsHumansMalignancyExtractInfectionSupplementationImportant roleTranscriptomic analysis of human IL‐7 receptor alpha low and high effector memory CD8+ T cells reveals an age‐associated signature linked to influenza vaccine response in older adults
Park H, Shin MS, Kim M, Bilsborrow JB, Mohanty S, Montgomery RR, Shaw AC, You S, Kang I. Transcriptomic analysis of human IL‐7 receptor alpha low and high effector memory CD8+ T cells reveals an age‐associated signature linked to influenza vaccine response in older adults. Aging Cell 2019, 18: e12960. PMID: 31044512, PMCID: PMC6612637, DOI: 10.1111/acel.12960.Peer-Reviewed Original ResearchConceptsPeripheral blood cellsPeripheral blood mononuclear cellsEffector memory CD8Influenza vaccine responsesEM CD8T cellsIL-7RαMemory CD8Vaccine responsesBlood cellsOlder adultsIL-7 receptor alphaSignature genesBlood mononuclear cellsHuman peripheral whole bloodAge-associated expansionPeripheral whole bloodGene expression profilesAge-associated changesMeta-analysis studyGlobal transcriptomic profilesMononuclear cellsCD8Receptor alphaExpression profilesTranscriptomic analysis of human IL-7 receptor alphalow and higheffector memory CD8+ T cells reveals an age-associated signature linked to influenza vaccine response in older adults
Park H, Shin M, Kim M, Bilsborrow J, Mohanty S, Montgomery R, Shaw A, Yoo S, Kang I. Transcriptomic analysis of human IL-7 receptor alphalow and higheffector memory CD8+ T cells reveals an age-associated signature linked to influenza vaccine response in older adults. The Journal Of Immunology 2019, 202: 181.22-181.22. DOI: 10.4049/jimmunol.202.supp.181.22.Peer-Reviewed Original ResearchPeripheral blood cellsPeripheral blood mononuclear cellsInfluenza vaccine responsesT cellsEM CD8Memory CD8Vaccine responsesOlder adultsBlood cellsSignature genesEffector memory CD8Blood mononuclear cellsHuman peripheral whole bloodAge-associated expansionPeripheral whole bloodGene expression profilesAge-associated changesMeta-analysis studyGlobal transcriptomic profilesMononuclear cellsCD8Expression profilesSignificant associationTranscription factorsWhole bloodEstrogen receptor α in T cells suppresses follicular helper T cell responses and prevents autoimmunity
Kim D, Park H, Park H, Lee J, Ko C, Gye M, Choi J. Estrogen receptor α in T cells suppresses follicular helper T cell responses and prevents autoimmunity. Experimental & Molecular Medicine 2019, 51: 1-9. PMID: 30988419, PMCID: PMC6465332, DOI: 10.1038/s12276-019-0237-z.Peer-Reviewed Original ResearchConceptsSheep red blood cellsKO miceT cellsTfh cellsTfh responsesAutoantibody productionFollicular helper T cell responsesHigh-affinity antigen-specific antibodiesCell responsesFollicular helper T cellsHelper T cell responsesERα KO miceTfh cell responsesMesenteric lymph nodesT cell responsesHelper T cellsGerminal center responseERα knockout miceWild-type miceAntigen-specific antibodiesYears of ageEstrogen receptor alphaEstrogen receptor αIsotype class switchingTreg cellsDissecting alterations in human CD8+ T cells with aging by high-dimensional single cell mass cytometry
Shin MS, Yim K, Moon K, Park HJ, Mohanty S, Kim JW, Montgomery RR, Shaw AC, Krishnaswamy S, Kang I. Dissecting alterations in human CD8+ T cells with aging by high-dimensional single cell mass cytometry. Clinical Immunology 2019, 200: 24-30. PMID: 30659916, PMCID: PMC6443094, DOI: 10.1016/j.clim.2019.01.005.Peer-Reviewed Original Research
2018
Macrophage Migration Inhibitory Factor Regulates U1 Small Nuclear RNP Immune Complex–Mediated Activation of the NLRP3 Inflammasome
Shin MS, Kang Y, Wahl ER, Park HJ, Lazova R, Leng L, Mamula M, Krishnaswamy S, Bucala R, Kang I. Macrophage Migration Inhibitory Factor Regulates U1 Small Nuclear RNP Immune Complex–Mediated Activation of the NLRP3 Inflammasome. Arthritis & Rheumatology 2018, 71: 109-120. PMID: 30009530, PMCID: PMC6310104, DOI: 10.1002/art.40672.Peer-Reviewed Original ResearchMeSH KeywordsAntigen-Antibody ComplexAutoantibodiesBlotting, WesternCARD Signaling Adaptor ProteinsEnzyme-Linked Immunosorbent AssayFlow CytometryHumansInflammasomesInterleukin-1betaIntramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsMass SpectrometryMonocytesNLR Family, Pyrin Domain-Containing 3 ProteinReceptors, ImmunologicRibonucleoprotein, U1 Small NuclearConceptsMacrophage migration inhibitory factorSystemic lupus erythematosusMigration inhibitory factorNLRP3 inflammasome activationImmune complexesIL-1βNLRP3 inflammasomeHuman monocytesInflammasome activationExpression of MIFProduction of MIFInhibitory factorCaspase-1IL-1β levelsIL-1β productionEnzyme-linked immunosorbentQuantitative polymerase chain reactionHigh expression alleleLupus patientsMIF productionMIF receptorInflammatory characteristicsLupus erythematosusInterleukin-1βPolymerase chain reaction