2021
Tet2 Controls the Responses of β cells to Inflammation in Autoimmune Diabetes
Rui J, Deng S, Perdigoto AL, Ponath G, Kursawe R, Lawlor N, Sumida T, Levine-Ritterman M, Stitzel ML, Pitt D, Lu J, Herold KC. Tet2 Controls the Responses of β cells to Inflammation in Autoimmune Diabetes. Nature Communications 2021, 12: 5074. PMID: 34417463, PMCID: PMC8379260, DOI: 10.1038/s41467-021-25367-z.Peer-Reviewed Original ResearchConceptsImmune cellsΒ-cellsNOD/SCID recipientsDiabetogenic immune cellsDiabetogenic T cellsBone marrow transplantType 1 diabetesExpression of TET2Human β-cellsIslet infiltratesSCID recipientsMarrow transplantInflammatory pathwaysTransfer of diseaseT cellsInflammatory genesImmune killingPathologic interactionsReduced expressionDiabetesInflammationTET2MiceRecipientsCells
2017
β Cells that Resist Immunological Attack Develop during Progression of Autoimmune Diabetes in NOD Mice
Rui J, Deng S, Arazi A, Perdigoto AL, Liu Z, Herold KC. β Cells that Resist Immunological Attack Develop during Progression of Autoimmune Diabetes in NOD Mice. Cell Metabolism 2017, 25: 727-738. PMID: 28190773, PMCID: PMC5342930, DOI: 10.1016/j.cmet.2017.01.005.Peer-Reviewed Original ResearchConceptsΒ-cellsImmune attackNon-obese diabetic (NOD) miceImmune inhibitory markersProgression of T1DChronic autoimmune diseaseType 1 diabetesLong-term survivalNormal β-cellsHuman β-cellsIslet infiltratesAutoimmune diabetesNOD miceDiabetic miceAutoimmune diseasesInhibitory markersImmune cellsImmune responseDiabetesStemness genesΒ cell identity genesSimilar changesCell deathDiseaseMice
2016
Characterization of Diabetogenic CD8+ T Cells IMMUNE THERAPY WITH METABOLIC BLOCKADE*
Garyu JW, Uduman M, Stewart A, Rui J, Deng S, Shenson J, Staron MM, Kaech SM, Kleinstein SH, Herold KC. Characterization of Diabetogenic CD8+ T Cells IMMUNE THERAPY WITH METABOLIC BLOCKADE*. Journal Of Biological Chemistry 2016, 291: 11230-11240. PMID: 26994137, PMCID: PMC4900270, DOI: 10.1074/jbc.m115.713362.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD8-Positive T-LymphocytesDiabetes Mellitus, Type 1InsulinIslets of LangerhansMice, Inbred NODMice, TransgenicPrediabetic StateConceptsPrediabetic NOD miceNOD miceT cellsDiabetogenic CD8Reactive cellsMemory precursor effector cellsType 1 diabetes mellitusΒ-cellsGlucose tolerance deterioratesAutoreactive T cellsHyperglycemic NOD miceInsulin-producing β-cellsAutoimmune effectorsAutoimmune diabetesReactive CD8Glucose intoleranceDiabetes mellitusEffector cellsImmune therapyMetabolic disturbancesTolerance deterioratesDisease progressionInsulin pelletsSubset of cellsConventional antigensMethylation of insulin DNA in response to proinflammatory cytokines during the progression of autoimmune diabetes in NOD mice
Rui J, Deng S, Lebastchi J, Clark PL, Usmani-Brown S, Herold KC. Methylation of insulin DNA in response to proinflammatory cytokines during the progression of autoimmune diabetes in NOD mice. Diabetologia 2016, 59: 1021-1029. PMID: 26910463, PMCID: PMC4826795, DOI: 10.1007/s00125-016-3897-4.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsCytokinesDiabetes Mellitus, Type 1DNADNA MethylationFemaleHumansInsulinInsulin-Secreting CellsMiceMice, Inbred NODConceptsInsulin gene expressionGene expressionQuantitative real-time RT-PCRMethylation marksInsulin geneNOD miceBeta cellsDNA methyltransferasesDisease progressionAims/hypothesisType 1 diabetesIns2 geneInsulin DNAMethylationReal-time RT-PCRGenesBeta-cell functionExon 1Human beta cellsBeta-cell massPancreatic beta cellsType 1 diabetesMethyltransferasesEffects of cytokinesExon 2Cell mass
2015
A Preclinical Consortium Approach for Assessing the Efficacy of Combined Anti-CD3 Plus IL-1 Blockade in Reversing New-Onset Autoimmune Diabetes in NOD Mice
Gill RG, Pagni PP, Kupfer T, Wasserfall CH, Deng S, Posgai A, Manenkova Y, Hani A, Straub L, Bernstein P, Atkinson MA, Herold KC, von Herrath M, Staeva T, Ehlers MR, Nepom GT. A Preclinical Consortium Approach for Assessing the Efficacy of Combined Anti-CD3 Plus IL-1 Blockade in Reversing New-Onset Autoimmune Diabetes in NOD Mice. Diabetes 2015, 65: 1310-1316. PMID: 26718498, PMCID: PMC5860426, DOI: 10.2337/db15-0492.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalAutoimmune DiseasesBiomedical ResearchCD3 ComplexDiabetes Mellitus, Type 1Drug Administration ScheduleDrug Therapy, CombinationFemaleImmunoglobulin Fab FragmentsImmunotherapyInsulinInsulin SecretionInsulin-Secreting CellsInterleukin-1 Receptor Accessory ProteinInterleukin-1betaMice, Inbred NODMulticenter Studies as TopicPilot ProjectsReceptors, Interleukin-1 Type IRecombinant Fusion ProteinsReproducibility of ResultsResearch DesignSpecific Pathogen-Free OrganismsUnited StatesConceptsNew-onset diseaseIL-1 blockadeAnti-CD3 treatmentNOD micePreclinical studiesInterleukin-1IL-1β monoclonal antibodyIslet β-cell massNOD mouse modelImmune Tolerance NetworkType 1 diabetesΒ-cell massApplicable immunotherapiesFuture clinical useStudy entryProspective studyClinical trialsMouse modelMulticenter consortiumAnimal modelsCandidate therapeuticsClinical useTherapeutic agentsMonoclonal antibodiesDisease
2013
Immune Therapy and β-Cell Death in Type 1 Diabetes
Lebastchi J, Deng S, Lebastchi AH, Beshar I, Gitelman S, Willi S, Gottlieb P, Akirav EM, Bluestone JA, Herold KC. Immune Therapy and β-Cell Death in Type 1 Diabetes. Diabetes 2013, 62: 1676-1680. PMID: 23423576, PMCID: PMC3636605, DOI: 10.2337/db12-1207.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntibodies, Monoclonal, HumanizedCD3 ComplexC-PeptideCytotoxicity Tests, ImmunologicCytotoxicity, ImmunologicDiabetes Mellitus, Type 1DNA MethylationFemaleHumansHypoglycemic AgentsImmunologic FactorsImmunotherapyInsulinInsulin SecretionInsulin-Secreting CellsIslets of LangerhansMalePostprandial PeriodYoung AdultConceptsRecent-onset T1DΒ-cell deathΒ-cellsNondiabetic subjectsImmune therapyType 1 diabetes resultsAnti-CD3 monoclonal antibodyUnmethylated INS DNAC-peptide responseNondiabetic control subjectsΒ-cell functionInsulin-producing β-cellsHigh rateImmune interventionDiabetes resultsControl subjectsClinical trialsPatientsT1DType 1Monoclonal antibodiesDeathTeplizumabINS DNATherapy
2012
Teplizumab Induces Human Gut-Tropic Regulatory Cells in Humanized Mice and Patients
Waldron-Lynch F, Henegariu O, Deng S, Preston-Hurlburt P, Tooley J, Flavell R, Herold KC. Teplizumab Induces Human Gut-Tropic Regulatory Cells in Humanized Mice and Patients. Science Translational Medicine 2012, 4: 118ra12. PMID: 22277969, PMCID: PMC4131554, DOI: 10.1126/scitranslmed.3003401.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, Monoclonal, HumanizedCD3 ComplexCell MovementDiabetes Mellitus, Type 1Forkhead Transcription FactorsGastrointestinal TractHumansHypoglycemic AgentsInterleukin-10Intestine, SmallL-SelectinMiceMucous MembraneNatalizumabOligonucleotide Array Sequence AnalysisReceptors, CCR6T-Lymphocytes, RegulatoryConceptsHumanized micePeripheral circulationSmall intestineType 1 diabetes mellitusNovel immunologic mechanismIL-10 expressionTreatment of patientsType 1 diabetesSecondary lymph organsHuman immune cellsT cell migrationMechanism of actionGut-tropicImmunologic mechanismsRegulatory cellsDiabetes mellitusImmune therapyInterleukin-10Immune cellsRegulatory cytokinesClinical trialsPreclinical modelsClinical studiesT cellsHuman hematopoietic stem cells
2008
Anti‐CD20 Treatment Prolongs Syngeneic Islet Graft Survival and Delays the Onset of Recurrent Autoimmune Diabetes
Hu C, Deng S, Wong FS, Wen L. Anti‐CD20 Treatment Prolongs Syngeneic Islet Graft Survival and Delays the Onset of Recurrent Autoimmune Diabetes. Annals Of The New York Academy Of Sciences 2008, 1150: 217-219. PMID: 19120299, DOI: 10.1196/annals.1447.032.Peer-Reviewed Original ResearchConceptsImmunosuppressive drug treatmentType 1 diabetesIslet transplantationDrug treatmentLong-term immunosuppressive drug treatmentSyngeneic islet graft survivalB cell depletion therapyT cell-mediated destructionAccepted therapeutic optionB-cell depletionPancreatic islet beta cellsCell-mediated destructionIslet graft survivalSyngeneic islet transplantationPancreatic islet transplantationIslet beta cellsRecurrent AutoimmuneTolerance establishmentGraft survivalNOD miceTherapeutic optionsAutoimmune diseasesCell depletionInsulin treatmentBeta cells