2016
Dendritic cells maintain dermal adipose–derived stromal cells in skin fibrosis
Chia JJ, Zhu T, Chyou S, Dasoveanu DC, Carballo C, Tian S, Magro CM, Rodeo S, Spiera RF, Ruddle NH, McGraw TE, Browning JL, Lafyatis R, Gordon JK, Lu TT. Dendritic cells maintain dermal adipose–derived stromal cells in skin fibrosis. Journal Of Clinical Investigation 2016, 126: 4331-4345. PMID: 27721238, PMCID: PMC5096920, DOI: 10.1172/jci85740.Peer-Reviewed Original ResearchConceptsAdipose-derived mesenchymal stromal cellsDendritic cellsSkin fibrosisDermal white adipose tissueFibrotic skinAdipose tissueStromal cellsMesenchymal stromal cell therapyScleroderma skin fibrosisStromal cell therapyWhite adipose tissueAdipose-derived stromal cellsMesenchymal stromal cellsΒ expressionMurine modelEffective treatmentFibrosisΒ1-integrin pathwayReparative functionsCell therapySclerodermaSkin functionIntegrin pathwaySurvivalAtrophyThe lymphotoxin β receptor is a potential therapeutic target in renal inflammation
Seleznik G, Seeger H, Bauer J, Fu K, Czerkowicz J, Papandile A, Poreci U, Rabah D, Ranger A, Cohen CD, Lindenmeyer M, Chen J, Edenhofer I, Anders HJ, Lech M, Wüthrich RP, Ruddle NH, Moeller MJ, Kozakowski N, Regele H, Browning JL, Heikenwalder M, Segerer S. The lymphotoxin β receptor is a potential therapeutic target in renal inflammation. Kidney International 2016, 89: 113-126. PMID: 26398497, DOI: 10.1038/ki.2015.280.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsCell LineChemokinesDisease Models, AnimalEpithelial CellsFemaleGlomerulonephritis, IGAHumansImmunoglobulinsKidney GlomerulusKidney TubulesLigandsLupus NephritisLymphocytesLymphotoxin beta ReceptorLymphotoxin-alphaLymphotoxin-betaMaleMesangial CellsMiceMiddle AgedRNA, MessengerSignal TransductionTranscriptomeConceptsTubular epithelial cellsParietal epithelial cellsEpithelial cellsRenal injuryLTβR signalingTherapeutic targetGlomerular immune complex depositionLymphotoxin β receptor (LTβR) signalingImproved renal functionSerum autoantibody titersHuman tubular epithelial cellsImmune complex depositionMurine lupus modelsProgressive kidney diseaseSuitable therapeutic targetPreclinical mouse modelsDifferent renal compartmentsPotential therapeutic targetΒ Receptor SignalingLymphotoxin β receptorAutoantibody titersRenal inflammationLupus modelsRenal functionRenal biopsy
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 modelsInsulitisCell-selective knockout and 3D confocal image analysis reveals separate roles for astrocyte-and endothelial-derived CCL2 in neuroinflammation
Paul D, Ge S, Lemire Y, Jellison ER, Serwanski DR, Ruddle NH, Pachter JS. Cell-selective knockout and 3D confocal image analysis reveals separate roles for astrocyte-and endothelial-derived CCL2 in neuroinflammation. Journal Of Neuroinflammation 2014, 11: 10. PMID: 24444311, PMCID: PMC3906899, DOI: 10.1186/1742-2094-11-10.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalomyelitisBlood-brain barrierCentral nervous systemBrain microvascular endothelial cellsKO miceEarly experimental autoimmune encephalomyelitisMyelin oligodendrocyte glycoprotein peptideEndothelial cellsNormal central nervous systemReduced EAE severityClinical disease progressionIFN-γ productionT cell proliferationWild-type miceMicrovascular endothelial cellsCCL2 immunoreactivityEAE severityImmunofluorescence confocal microscopyBBB damageEAE modelAutoimmune encephalomyelitisIL-17Neuroinflammatory conditionsNeuroinflammatory diseasesWT mice
2012
Tertiary lymphoid organ development coincides with determinant spreading of the myelin-specific T cell response
Kuerten S, Schickel A, Kerkloh C, Recks MS, Addicks K, Ruddle NH, Lehmann PV. Tertiary lymphoid organ development coincides with determinant spreading of the myelin-specific T cell response. Acta Neuropathologica 2012, 124: 861-873. PMID: 22842876, DOI: 10.1007/s00401-012-1023-3.Peer-Reviewed Original ResearchConceptsTertiary lymphoid organsExperimental autoimmune encephalomyelitisMyelin-specific T cell responseCentral nervous systemB cell aggregatesT cell responsesMultiple sclerosisB cell aggregationDeterminant spreadingB cellsCell responsesActive immune responseMyelin basic proteinLymphoid neogenesisAutoimmune encephalomyelitisMS patientsAggressive diseaseAutoimmune pathologyPatient populationLymphoid organsDisease onsetDisease progressionT cellsImmune responsePathogenic contribution
2010
Focal experimental autoimmune encephalomyelitis in the lewis rat induced by immunization with myelin oligodendrocyte glycoprotein and intraspinal injection of vascular endothelial growth factor
Sasaki M, Lankford KL, Brown RJ, Ruddle NH, Kocsis JD. Focal experimental autoimmune encephalomyelitis in the lewis rat induced by immunization with myelin oligodendrocyte glycoprotein and intraspinal injection of vascular endothelial growth factor. Glia 2010, 58: 1523-1531. PMID: 20645414, DOI: 10.1002/glia.21026.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceAnimalsAntibodiesBlood-Brain BarrierCD3 ComplexDisease Models, AnimalEncephalomyelitis, Autoimmune, ExperimentalEnzyme-Linked Immunosorbent AssayFemaleFreund's AdjuvantInjections, SpinalLipidsMicroscopy, Electron, TransmissionMyelin ProteinsMyelin-Associated GlycoproteinMyelin-Oligodendrocyte GlycoproteinRatsRats, Inbred LewSpinal CordTime FactorsVascular Endothelial Growth Factor AConceptsMyelin oligodendrocyte glycoproteinVascular endothelial growth factorExperimental autoimmune encephalomyelitisIncomplete Freund's adjuvantBlood-brain barrierInflammatory demyelinating lesionsLewis ratsEndothelial growth factorDemyelinating lesionsEAE modelAutoimmune encephalomyelitisFreund's adjuvantIntraspinal injectionOligodendrocyte glycoproteinRecombinant rat myelin oligodendrocyte glycoproteinCentral nervous system locationsGrowth factorSensitized T cellsFocal experimental autoimmune encephalomyelitisRat myelin oligodendrocyte glycoproteinSite of injectionMyelin-forming cellsMOG immunizationExtensive demyelinationLymphocyte infiltration
2009
Depletion of CD4+CD25+ T cells exacerbates experimental autoimmune encephalomyelitis induced by mouse, but not rat, antigens
Akirav EM, Bergman CM, Hill M, Ruddle NH. Depletion of CD4+CD25+ T cells exacerbates experimental autoimmune encephalomyelitis induced by mouse, but not rat, antigens. Journal Of Neuroscience Research 2009, 87: 3511-3519. PMID: 19125411, PMCID: PMC4429897, DOI: 10.1002/jnr.21981.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigensAutoantigensAutoimmunityBiomarkersCD4 AntigensCD4-Positive T-LymphocytesCells, CulturedCentral Nervous SystemChemotaxis, LeukocyteDisease Models, AnimalEncephalomyelitis, Autoimmune, ExperimentalFemaleInterferon-gammaInterleukin-10Interleukin-17Interleukin-2 Receptor alpha SubunitLymphocyte ActivationMiceMice, Inbred C57BLMultiple SclerosisMyelin ProteinsMyelin-Associated GlycoproteinMyelin-Oligodendrocyte GlycoproteinRatsT-Lymphocytes, RegulatoryConceptsExperimental autoimmune encephalomyelitisMyelin oligodendrocyte glycoproteinAutoimmune encephalomyelitisT cellsIL-10-producing cellsRegulatory T cellsTissue-restricted antigensCentral nervous systemField of autoimmunityT cell activationTreg depletionEAE severitySelf antigensOligodendrocyte glycoproteinForeign antigensExperimental diseaseNervous systemRelated antigensMiceSelf-antigen specificityAntigenTregsEncephalomyelitisAutoimmunityRats