2022
A multiple sclerosis–protective coding variant reveals an essential role for HDAC7 in regulatory T cells
Axisa P, Yoshida T, Lucca L, Kasler H, Lincoln M, Pham G, Del Priore D, Carpier J, Lucas C, Verdin E, Sumida T, Hafler D. A multiple sclerosis–protective coding variant reveals an essential role for HDAC7 in regulatory T cells. Science Translational Medicine 2022, 14: eabl3651. PMID: 36516268, DOI: 10.1126/scitranslmed.abl3651.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalitisRegulatory T cellsHistone deacetylase 7Multiple sclerosisT cellsMouse modelFunction of Foxp3CD4 T cellsHigher suppressive capacityVivo modelingAutoimmune encephalitisEAE severityImmunosuppressive subsetAutoimmune diseasesImmunomodulatory roleSuppressive capacityImmune cellsDisease onsetDistinct molecular classesSusceptibility lociGenetic susceptibility lociSingle-cell RNA sequencingDisease riskPatient samplesProtective variants“Near Cure” treatment of severe acute EAE in MIF-1-deficient female and male mice with a bifunctional MHCII-derived molecular construct
Vandenbark AA, Meza-Romero R, Wiedrick J, Gerstner G, Seifert H, Kent G, Piechycna M, Benedek G, Bucala R, Offner H. “Near Cure” treatment of severe acute EAE in MIF-1-deficient female and male mice with a bifunctional MHCII-derived molecular construct. Cellular Immunology 2022, 378: 104561. PMID: 35738135, PMCID: PMC9714992, DOI: 10.1016/j.cellimm.2022.104561.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalomyelitisAcute experimental autoimmune encephalomyelitisDRα1-MOG-35Multiple sclerosisMIF-1EAE scoresMale miceMIF-2Severe diseaseMacrophage migration inhibitory factorClinical EAE scoresMIF-deficient micePeripheral inflammatory cellsMigration inhibitory factorSpinal cord tissueT cell activationSex-dependent differencesEAE severityAutoimmune encephalomyelitisSerum levelsTreatment of WTInflammatory cellsFemale miceClinical signsCord tissue
2021
Dectin-1 limits CNS autoimmunity through a non-canonical pathway
Deerhake M, Danzaki K, Inoue M, Cardakli E, Nonaka T, Aggarwal N, Barclay W, Ji R, Shinohara M. Dectin-1 limits CNS autoimmunity through a non-canonical pathway. The Journal Of Immunology 2021, 206: 96.07-96.07. DOI: 10.4049/jimmunol.206.supp.96.07.Peer-Reviewed Original ResearchExperimental autoimmune encephalomyelitisC-type lectin receptorsCentral nervous systemMultiple sclerosisInnate immunityDectin-1 pathwayCNS autoimmunityEAE severityAutoimmune encephalomyelitisNeuroprotective cytokineNeuroprotective functionNeurologic disordersPathologic roleImmune responseAnimal modelsNervous systemMyeloid cellsOSM receptorNon-canonical pathwayUpregulated expressionOncostatin MLectin receptorsAutoimmunityRNA-seq profilingProtective aspectsDectin-1 limits autoimmune neuroinflammation and promotes myeloid cell-astrocyte crosstalk via Card9-independent expression of Oncostatin M
Deerhake ME, Danzaki K, Inoue M, Cardakli ED, Nonaka T, Aggarwal N, Barclay WE, Ji RR, Shinohara ML. Dectin-1 limits autoimmune neuroinflammation and promotes myeloid cell-astrocyte crosstalk via Card9-independent expression of Oncostatin M. Immunity 2021, 54: 484-498.e8. PMID: 33581044, PMCID: PMC7956124, DOI: 10.1016/j.immuni.2021.01.004.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAstrocytesBrainCARD Signaling Adaptor ProteinsCell CommunicationCells, CulturedDisease Models, AnimalEncephalomyelitis, Autoimmune, ExperimentalGalectinsGene Expression RegulationLectins, C-TypeMice, Inbred C57BLMice, KnockoutMultiple SclerosisMyelin-Oligodendrocyte GlycoproteinMyeloid CellsNeurogenic InflammationOncostatin MOncostatin M Receptor beta SubunitPeptide FragmentsReceptors, MitogenSignal TransductionConceptsExperimental autoimmune encephalomyelitisC-type lectin receptorsCentral nervous systemAutoimmune neuroinflammationOncostatin MPro-resolution functionHeat-killed mycobacteriaDectin-1 pathwayDectin-1 ligandsPotential therapeutic targetEAE severityAutoimmune encephalomyelitisNeuroprotective moleculesNeurologic disordersPathologic roleGalectin-9Therapeutic targetTranscription factor NFATNervous systemMyeloid cellsInnate immunityOSM receptorLectin receptorsEnhanced gene expressionNeuroinflammation
2014
Cell-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
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
2007
Regulatory T cells selectively protect against experimental autoimmune encephalomyelitis induced with self but not foreign antigens (B79)
Akirav E, Xu Y, Bergman C, Hill M, Ruddle N. Regulatory T cells selectively protect against experimental autoimmune encephalomyelitis induced with self but not foreign antigens (B79). The Journal Of Immunology 2007, 178: lb16-lb17. DOI: 10.4049/jimmunol.178.supp.b79.Peer-Reviewed Original ResearchMouse myelin oligodendrocyte glycoproteinExperimental autoimmune encephalomyelitisMyelin oligodendrocyte glycoproteinRegulatory T cellsTreg depletionT cellsAutoimmune encephalomyelitisMultiple sclerosisHuman myelin oligodendrocyte glycoproteinRatio of IFNγT cell responsesT cell proliferationCentral nervous systemEAE severityMOG35-55IL17 productionAutoimmune diseasesOligodendrocyte glycoproteinForeign antigensMurine modelNervous systemRelated antigensDisease severityCell responsesMice
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