2024
The immunology of type 1 diabetes
Herold K, Delong T, Perdigoto A, Biru N, Brusko T, Walker L. The immunology of type 1 diabetes. Nature Reviews Immunology 2024, 24: 435-451. PMID: 38308004, PMCID: PMC7616056, DOI: 10.1038/s41577-023-00985-4.Peer-Reviewed Original ResearchType 1 diabetesT cellsDestruction of pancreatic B-cellsImmune-targeted interventionsTarget T cellsPathogenesis of T1DB-cell massPancreatic B-cellsAutoimmune destructionB cellsGlucose dysregulationImmune mechanismsImmune systemNatural historyDisease pathogenesisT1DRegulatory approvalTreatment of individualsDiscovery of insulinPathogenesisDiseaseSeminal discoveriesImmunotherapy
2022
Immune cells and their inflammatory mediators modify beta cells and cause checkpoint inhibitor-induced diabetes
Perdigoto AL, Deng S, Du KC, Kuchroo M, Burkhardt DB, Tong A, Israel G, Robert ME, Weisberg SP, Kirkiles-Smith N, Stamatouli AM, Kluger HM, Quandt Z, Young A, Yang ML, Mamula MJ, Pober JS, Anderson MS, Krishnaswamy S, Herold KC. Immune cells and their inflammatory mediators modify beta cells and cause checkpoint inhibitor-induced diabetes. JCI Insight 2022, 7: e156330. PMID: 35925682, PMCID: PMC9536276, DOI: 10.1172/jci.insight.156330.Peer-Reviewed Original ResearchConceptsCheckpoint inhibitorsΒ-cellsPD-1/PD-L1 pathwayT-lymphocyte antigen-4PD-1 blockadePD-L1 pathwayDeath ligand 1NOD mouse modelDevelopment of diabetesHuman β-cellsAutoimmune complicationsNOD miceΒ-cell populationDeath-1Diabetes mellitusImmune infiltratesInflammatory mediatorsPancreatic inflammationPD-L1Induced diabetesLymphocytic infiltrationInflammatory cytokinesAntigen-4Immune cellsT cellsCitrullination of glucokinase is linked to autoimmune diabetes
Yang ML, Horstman S, Gee R, Guyer P, Lam TT, Kanyo J, Perdigoto AL, Speake C, Greenbaum CJ, Callebaut A, Overbergh L, Kibbey RG, Herold KC, James EA, Mamula MJ. Citrullination of glucokinase is linked to autoimmune diabetes. Nature Communications 2022, 13: 1870. PMID: 35388005, PMCID: PMC8986778, DOI: 10.1038/s41467-022-29512-0.Peer-Reviewed Original ResearchConceptsGlucose-stimulated insulin secretionResult of inflammationType 1 diabetesBeta-cell metabolismPancreatic beta cellsAutoimmune diabetesNOD miceAutoreactive CD4Inflammatory cytokinesAutoimmune biomarkersInsulin secretionT cellsBeta cellsType 1InflammationBiologic activityReactive oxygen speciesDiabetesPost-translational modificationsDiabetes biomarkersGlycogen synthesisBiomarkersCitrullinationGlucokinaseOxygen species
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 expressionDiabetesInflammationTET2MiceRecipientsCellsAdverse events induced by immune checkpoint inhibitors
Perdigoto AL, Kluger H, Herold KC. Adverse events induced by immune checkpoint inhibitors. Current Opinion In Immunology 2021, 69: 29-38. PMID: 33640598, PMCID: PMC8122053, DOI: 10.1016/j.coi.2021.02.002.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoantibodiesAutoantigensAutoimmune DiseasesAutoimmunityCytotoxicity, ImmunologicDrug-Related Side Effects and Adverse ReactionsGene-Environment InteractionGenetic Predisposition to DiseaseHumansImmune Checkpoint InhibitorsImmunotherapyLymphocyte ActivationNeoplasmsT-LymphocytesConceptsImmune checkpoint inhibitorsCheckpoint inhibitorsAdverse eventsT cellsImmune related adverse eventsEmergence of autoantibodiesRelated adverse eventsAnti-tumor responseAutoreactive T cellsActivated T cellsAutoimmune mechanismsTreatment of cancerAutoimmune diseasesInflammatory responsePredictive valueHost factorsToxic effectsInhibitorsDirect effectOngoing investigationAutoantibodiesCellsAutoimmunityPathogenesisCancer
2018
Treatment of type 1 diabetes with teplizumab: clinical and immunological follow-up after 7 years from diagnosis
Perdigoto AL, Preston-Hurlburt P, Clark P, Long SA, Linsley PS, Harris KM, Gitelman SE, Greenbaum CJ, Gottlieb PA, Hagopian W, Woodwyk A, Dziura J, Herold KC. Treatment of type 1 diabetes with teplizumab: clinical and immunological follow-up after 7 years from diagnosis. Diabetologia 2018, 62: 655-664. PMID: 30569273, PMCID: PMC6402971, DOI: 10.1007/s00125-018-4786-9.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAntibodies, Monoclonal, HumanizedArea Under CurveAutoimmunityCD3 ComplexCD8-Positive T-LymphocytesChildC-PeptideCytokinesDiabetes Mellitus, Type 1FemaleFollow-Up StudiesHumansHypoglycemic AgentsInsulinIslets of LangerhansMaleRandomized Controlled Trials as TopicRemission InductionTreatment OutcomeYoung AdultConceptsC-peptide responseType 1 diabetesMixed meal tolerance testDetectable C-peptideC-peptideInsulin useTolerance testT cellsControl groupNew-onset type 1 diabetesPeripheral blood mononuclear cellsConclusions/interpretationThese findingsAnti-CD3 monoclonal antibodyDaily insulin useBlood mononuclear cellsDiagnosis of diabetesSuccessful immune therapiesOriginal control groupCell death proteinAnergic CD8ResultsFifty-sixImmune therapyInterpretationThese findingsMononuclear cellsCytokine release