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
2019
Multiplexed imaging of immune cells in staged multiple sclerosis lesions by mass cytometry
Ramaglia V, Sheikh-Mohamed S, Legg K, Park C, Rojas OL, Zandee S, Fu F, Ornatsky O, Swanson EC, Pitt D, Prat A, McKee TD, Gommerman JL. Multiplexed imaging of immune cells in staged multiple sclerosis lesions by mass cytometry. ELife 2019, 8: e48051. PMID: 31368890, PMCID: PMC6707785, DOI: 10.7554/elife.48051.Peer-Reviewed Original ResearchConceptsMultiple sclerosisMS disease activityT-cell phenotypeMass cytometryTypes of lymphocytesMultiple sclerosis lesionsNatalizumab cessationDisease activityMS patientsInflammatory lesionsImmune cellsSpinal cordLesion morphometryMS lesionsB cellsLesion typeSclerosis lesionsLesionsBlood vesselsCell phenotypeFunctional stateCytometryCellular contentCell-cell interactionsPhenotype
2018
Enhanced astrocyte responses are driven by a genetic risk allele associated with multiple sclerosis
Ponath G, Lincoln MR, Levine-Ritterman M, Park C, Dahlawi S, Mubarak M, Sumida T, Airas L, Zhang S, Isitan C, Nguyen TD, Raine CS, Hafler DA, Pitt D. Enhanced astrocyte responses are driven by a genetic risk allele associated with multiple sclerosis. Nature Communications 2018, 9: 5337. PMID: 30559390, PMCID: PMC6297228, DOI: 10.1038/s41467-018-07785-8.Peer-Reviewed Original ResearchConceptsMultiple sclerosisAstrocyte responseRisk variantsLocal autoimmune inflammationPeripheral immune cellsCentral nervous system cellsPeripheral immune systemCultured human astrocytesNervous system cellsNF-κB signalingCNS accessDysfunctional lymphocytesAstroglial functionAutoimmune inflammationLymphocytic infiltrateLymphocyte recruitmentImmune cellsGenetic risk allelesGenetic risk variantsMS lesionsMS susceptibilityHuman astrocytesLesion sizeImmune systemSystem cellsSignificance and In Vivo Detection of Iron-Laden Microglia in White Matter Multiple Sclerosis Lesions
Gillen KM, Mubarak M, Nguyen TD, Pitt D. Significance and In Vivo Detection of Iron-Laden Microglia in White Matter Multiple Sclerosis Lesions. Frontiers In Immunology 2018, 9: 255. PMID: 29515576, PMCID: PMC5826076, DOI: 10.3389/fimmu.2018.00255.Peer-Reviewed Original ResearchConceptsCentral nervous systemChronic active lesionsMultiple sclerosisActive lesionsWhite matterWhite matter MS lesionsQuantitative susceptibility mappingNovel MS therapiesResident immune cellsChronic inflammatory activityWhite matter lesionsMyeloid cell activationAdjacent white matterWhite matter multiple sclerosis lesionsChronic tissue damageMultiple sclerosis lesionsMS therapyInflammatory activityMagnetic resonance imaging techniquesChronic inflammationMatter lesionsAged brainImmune cellsMyelin phagocytosisChronic diseases
2016
Myelin phagocytosis by astrocytes after myelin damage promotes lesion pathology
Ponath G, Ramanan S, Mubarak M, Housley W, Lee S, Sahinkaya FR, Vortmeyer A, Raine CS, Pitt D. Myelin phagocytosis by astrocytes after myelin damage promotes lesion pathology. Brain 2016, 140: 399-413. PMID: 28007993, PMCID: PMC5841057, DOI: 10.1093/brain/aww298.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnimalsAnimals, NewbornAstrocytesCell ProliferationCells, CulturedChild, PreschoolCultureCytokinesDemyelinating Autoimmune Diseases, CNSEndocytosisFemaleHumansHydrazonesMacrophagesMaleMiddle AgedMyelin SheathPhagocytosisRatsRats, Sprague-DawleyStrokeTime FactorsTransforming Growth Factor betaConceptsMyelin injuryMyelin phagocytosisMyelin debrisMultiple sclerosis lesionsMultiple sclerosisLesion pathologySclerosis lesionsAcute multiple sclerosis lesionsCentral nervous system pathologyProgressive multifocal leukoencephalopathyNervous system pathologySecretion of chemokinesNF-κB activationElevated chemokine expressionHypertrophic astrocytesMost astrocytesMyelin uptakeMultifocal leukoencephalopathyFirst-line responseAcute lesionsMyelin damageReactive astrocytesChemokine expressionAstroglial responseImmune cells
2000
Glutamate excitotoxicity — a mechanism for axonal damage and oligodendrocyte death in Multiple Sclerosis?
Werner P, Pitt D, Raine CS. Glutamate excitotoxicity — a mechanism for axonal damage and oligodendrocyte death in Multiple Sclerosis? Journal Of Neural Transmission. Supplementa 2000, 375-385. PMID: 11205156, DOI: 10.1007/978-3-7091-6301-6_27.Peer-Reviewed Original ResearchConceptsCentral nervous systemAMPA/kainate antagonistMultiple sclerosisGlutamate excitotoxicityImmune cellsKainate antagonistAxonal damageAntigen-primed T cellsMyelin-producing cellsLack of effectSite of entryCNS inflammationInflammatory attacksExperimental autoimmunePerivascular cuffsAutoimmune demyelinationInflammatory lesionsClinical differencesOligodendrocyte survivalEffective therapyGlutamate receptorsOligodendrocyte deathT cellsExcitotoxicityLesion size