2014
A Humanized Mouse Model of Autoimmune Insulitis
Milam A, Maher SE, Gibson JA, Lebastchi J, Wen L, Ruddle NH, Herold KC, Bothwell AL. A Humanized Mouse Model of Autoimmune Insulitis. Diabetes 2014, 63: 1712-1724. PMID: 24478396, PMCID: PMC3994947, DOI: 10.2337/db13-1141.Peer-Reviewed Original ResearchConceptsT cellsDiabetic donorsInsulin stainingMouse modelAntigen-pulsed cellsAutoantigen-derived peptidesNOD mouse modelHumanized mouse modelType 1 diabetesPancreatic β-cellsT cell linesHuman T cellsIslet infiltrationAutoimmune diabetesNOD-SCIDAutoimmune insulitisHuman diabetesDestructive infiltrationMouse isletsMechanism of inductionΒ-cellsDiabetesDiabetes researchDisease modelsInsulitis
2010
Prevention of Diabetes by FTY720-Mediated Stabilization of Peri-Islet Tertiary Lymphoid Organs
Penaranda C, Tang Q, Ruddle NH, Bluestone JA. Prevention of Diabetes by FTY720-Mediated Stabilization of Peri-Islet Tertiary Lymphoid Organs. Diabetes 2010, 59: 1461-1468. PMID: 20299465, PMCID: PMC2874707, DOI: 10.2337/db09-1129.Peer-Reviewed Original ResearchConceptsTertiary lymphoid organsPancreatic lymph nodesNOD miceLymph nodesDiabetes developmentDiabetic miceLymphoid organsSpontaneous type 1 diabetesB cell compartmentalizationExit of lymphocytesNonobese diabetic (NOD) miceAge-matched miceDevelopment of diabetesPrevention of diabetesNaive T cellsType 1 diabetesB cell compartmentWeeks of ageSignificant insulitisIslet destructionTreatment withdrawalAutoimmune destructionClinical scoresAccelerated diseaseDisease progression
2005
Chronic Lymphocytic Inflammation Specifies the Organ Tropism of Prions
Heikenwalder M, Zeller N, Seeger H, Prinz M, Klöhn P, Schwarz P, Ruddle NH, Weissmann C, Aguzzi A. Chronic Lymphocytic Inflammation Specifies the Organ Tropism of Prions. Science 2005, 307: 1107-1110. PMID: 15661974, DOI: 10.1126/science.1106460.Peer-Reviewed Original ResearchConceptsInflammatory conditionsNormal cellular prion protein PrPCCellular prion protein PrPCChronic lymphocytic inflammationIatrogenic prion transmissionChronic inflammatory conditionsPrion protein PrPCFDC-M1Lymphocytic inflammationEctopic inductionProinflammatory cytokinesInflamed organsImmune cellsInflammatory diseasesInflammatory fociLymphoid tissuePrion accumulationPrion inoculationOrgan tropismPrion pathogenesisPrion replicationTissue distributionPrion transmissionPrionsMice
1996
The Contribution of Insulitis to Diabetes Development in Tumor Necrosis Factor Transgenic Mice
Flavell RA, Kratz A, Ruddle NH. The Contribution of Insulitis to Diabetes Development in Tumor Necrosis Factor Transgenic Mice. Current Topics In Microbiology And Immunology 1996, 206: 33-50. PMID: 8608724, DOI: 10.1007/978-3-642-85208-4_3.Peer-Reviewed Original ResearchConceptsInsulin-dependent diabetes mellitusTumor necrosis factor-transgenic (TNF-Tg) miceDevelopment of diabetesHLA susceptibility allelesIslets of LangerhansHLA-DQβDiabetes mellitusFrank diabetesTransgenic miceStrong associationSusceptibility allelesDiabetesIdentical twinsDiseaseInsulinIsletsInsulitisSite of synthesisMellitusNumber of yearsPatientsMiceEnvironmental factors
1993
Transgenic tumor necrosis factor (TNF)-alpha production in pancreatic islets leads to insulitis, not diabetes. Distinct patterns of inflammation in TNF-alpha and TNF-beta transgenic mice.
Picarella DE, Kratz A, Li CB, Ruddle NH, Flavell RA. Transgenic tumor necrosis factor (TNF)-alpha production in pancreatic islets leads to insulitis, not diabetes. Distinct patterns of inflammation in TNF-alpha and TNF-beta transgenic mice. The Journal Of Immunology 1993, 150: 4136-50. PMID: 7682590, DOI: 10.4049/jimmunol.150.9.4136.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, SurfaceCD4 AntigensCD8 AntigensCell Adhesion MoleculesDiabetes Mellitus, Type 1Histocompatibility Antigens Class IIHumansIntercellular Adhesion Molecule-1Islets of LangerhansKidneyLeukocyte Common AntigensLymphotoxin-alphaMiceMice, Inbred NODMice, TransgenicPancreatitisProtein Tyrosine Phosphatase, Non-Receptor Type 1Receptors, Interleukin-2Tumor Necrosis Factor-alphaUp-RegulationConceptsTNF-alphaTransgenic miceTNF-alpha transgenic miceInsulin-dependent diabetes mellitusAdhesion molecules VCAM-1Rat insulin II promoterTNF-alpha transgeneRole of TNFMurine TNF-alphaTumor necrosis factorRegulation of inflammationMHC class IReduced insulin contentPeri-insulitisIslet destructionDiabetes mellitusAutoimmune diseasesAlpha productionIslet endotheliumNecrosis factorT cellsICAM-1VCAM-1Insulin contentB cellsProbing the mechanism of TNF-α(cachectin)- and TNF-β(lymphotoxin)-induced pancreatic inflammation with transgenic mice
Ruddle NH, Picarella D, Kratz A, Li C, Flavell RA. Probing the mechanism of TNF-α(cachectin)- and TNF-β(lymphotoxin)-induced pancreatic inflammation with transgenic mice. Research In Immunology 1993, 144: 336-342. PMID: 8278655, DOI: 10.1016/s0923-2494(93)80077-c.Peer-Reviewed Original Research
1992
Insulitis in transgenic mice expressing tumor necrosis factor beta (lymphotoxin) in the pancreas.
Picarella DE, Kratz A, Li CB, Ruddle NH, Flavell RA. Insulitis in transgenic mice expressing tumor necrosis factor beta (lymphotoxin) in the pancreas. Proceedings Of The National Academy Of Sciences Of The United States Of America 1992, 89: 10036-10040. PMID: 1279667, PMCID: PMC50272, DOI: 10.1073/pnas.89.21.10036.Peer-Reviewed Original ResearchConceptsNecrosis factor betaTransgenic miceFactor betaInsulin-dependent diabetes mellitusRat insulin II promoterTumor necrosis factor betaType 1 diabetesRegulation of inflammationTNF-beta geneDiabetes mellitusInflammatory infiltrateInflammatory diseasesT cellsImmune responseB cellsInsulitisDiabetesMicePancreasImportant early stepBetaEarly stagesCD8InfiltratesMellitus