2011
B Cells as a Therapeutic Target for IFN-β in Relapsing–Remitting Multiple Sclerosis
Ramgolam V, Sha Y, Marcus K, Choudhary N, Troiani L, Chopra M, Markovic-Plese S. B Cells as a Therapeutic Target for IFN-β in Relapsing–Remitting Multiple Sclerosis. The Journal Of Immunology 2011, 186: 4518-4526. PMID: 21368231, DOI: 10.4049/jimmunol.1000271.Peer-Reviewed Original ResearchConceptsRR-MS patientsIFN-β-1bRelapsing-remitting multiple sclerosisCell stimulatory capacityStimulatory capacityB cellsMS patientsUntreated patientsIL-23IL-27IL-12Multiple sclerosisIL-1βProliferative responseAg-specific T cell proliferative responsesFirst-line immunomodulatory therapyT cell proliferative responsesSuppression of CD40Low proliferative responseB-cell secretionCell proliferative responsesB cell functionMHC class IRR-MSImmunomodulatory therapy
2010
Interferon-beta inhibits Th17 cell differentiation in patients with multiple sclerosis.
Ramgolam V, Markovic-Plese S. Interferon-beta inhibits Th17 cell differentiation in patients with multiple sclerosis. Endocrine Metabolic & Immune Disorders - Drug Targets 2010, 10: 161-7. PMID: 20384573, DOI: 10.2174/187153010791213029.Peer-Reviewed Original ResearchConceptsDendritic cellsT cellsB cellsMultiple sclerosisCell-mediated autoimmune responseRetinoic acid-related orphan receptorTranscription factor retinoic acid-related orphan receptorAcid-related orphan receptorCytokines IL-17AFirst-line therapyCytokines IL-1bInduction of suppressorCell differentiationMechanism of actionRR-MSIL-17AIL-23Th17 cellsIL-10Immunoregulatory mechanismsIL-12Autoimmune responseAutoimmune diseasesCytokines interleukinChemokine receptors
2009
IFN-β Inhibits Human Th17 Cell Differentiation
Ramgolam V, Sha Y, Jin J, Zhang X, Markovic-Plese S. IFN-β Inhibits Human Th17 Cell Differentiation. The Journal Of Immunology 2009, 183: 5418-5427. PMID: 19783688, DOI: 10.4049/jimmunol.0803227.Peer-Reviewed Original ResearchMeSH KeywordsCD4-Positive T-LymphocytesCell DifferentiationCells, CulturedDendritic CellsDown-RegulationHumansInterferon beta-1aInterferon-betaInterleukin-10Interleukin-12 Subunit p35Interleukin-17Interleukin-1betaInterleukin-23 Subunit p19Multiple SclerosisNuclear Receptor Subfamily 1, Group F, Member 3PhosphorylationReceptors, CCR6Receptors, InterleukinReceptors, Retinoic AcidReceptors, Thyroid HormoneSTAT1 Transcription FactorSTAT3 Transcription FactorT-Lymphocytes, Helper-InducerUp-RegulationConceptsTh17 cell differentiationDendritic cellsMultiple sclerosisT cellsReceptor CIL-17AAutoimmune responseIL-1betaIFN beta-1a treatmentRelapsing-remitting multiple sclerosisIL-10 gene expressionTh17 cell markersUntreated MS patientsCNS inflammatory diseasesIL-10 secretionNaive T cellsTh17-polarizing conditionsEffect of IFNCell differentiationIL-27p28 expressionPrimary therapySuppressor of cytokineIL-17IL-23IL-23p19
2008
Simvastatin Inhibits IL-17 Secretion by Targeting Multiple IL-17-Regulatory Cytokines and by Inhibiting the Expression of IL-17 Transcription Factor RORC in CD4+ Lymphocytes
Zhang X, Jin J, Peng X, Ramgolam V, Markovic-Plese S. Simvastatin Inhibits IL-17 Secretion by Targeting Multiple IL-17-Regulatory Cytokines and by Inhibiting the Expression of IL-17 Transcription Factor RORC in CD4+ Lymphocytes. The Journal Of Immunology 2008, 180: 6988-6996. PMID: 18453621, DOI: 10.4049/jimmunol.180.10.6988.Peer-Reviewed Original ResearchMeSH KeywordsBlotting, WesternCD4-Positive T-LymphocytesCytokinesEnzyme-Linked Immunosorbent AssayFemaleFlow CytometryGene ExpressionHumansImmunologic FactorsInterleukin-17MaleMonocytesMultiple SclerosisNuclear ProteinsOligonucleotide Array Sequence AnalysisReceptors, Cytoplasmic and NuclearReverse Transcriptase Polymerase Chain ReactionSimvastatinSuppressor of Cytokine Signaling 3 ProteinSuppressor of Cytokine Signaling ProteinsT-Lymphocyte SubsetsConceptsAutoimmune responseMultiple sclerosisImmunomodulatory mechanismsT cellsIL-23 gene expressionTranscription factor RORCIL-17 productionIL-17 secretionIL-27 productionChronic inflammatory diseaseNovel immunomodulatory mechanismGood safety profileIL-17 transcriptionPromising therapeutic approachCholesterol-lowering agentsHuman autoimmune responseImmunomodulatory agentsSafety profileAutoimmune diseasesIL-6IL-4Inflammatory diseasesSpecific effectsTherapeutic approachesIFN-gammaDegenerate TCR recognition and dual DR2 restriction of autoreactive T cells: Implications for the initiation of the autoimmune response in multiple sclerosis
Zhang X, Tang Y, Sujkowska D, Wang J, Ramgolam V, Sospedra M, Adams J, Martin R, Pinilla C, Markovic‐Plese S. Degenerate TCR recognition and dual DR2 restriction of autoreactive T cells: Implications for the initiation of the autoimmune response in multiple sclerosis. European Journal Of Immunology 2008, 38: 1297-1309. PMID: 18412170, DOI: 10.1002/eji.200737519.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAmino Acid SequenceAutoimmunityClone CellsEpitopes, T-LymphocyteHLA-DR2 AntigenHumansInterferon-gammaInterleukin-17Interleukin-4Leukocytes, MononuclearLymphocyte ActivationMiddle AgedMultiple Sclerosis, Relapsing-RemittingMyelin Basic ProteinMyelin ProteinsMyelin Proteolipid ProteinMyelin-Associated GlycoproteinMyelin-Oligodendrocyte GlycoproteinPeptide FragmentsPeptidesReceptors, Antigen, T-CellT-Lymphocyte SubsetsT-LymphocytesConceptsMultiple sclerosisAutoimmune responseT cellsProliferative responseTCR degeneracyMHC class II allelesAutoreactive T cellsClass II allelesT cell activationMyelin peptidesMS patientsDR2 allelesHealthy controlsReactive cellsStimulatory potencyCell activationTCR recognitionCaucasian populationContext of diseaseSclerosisDR2aCellsILTCRPeptidesInterferon (IFN) beta ‐1a induces IL‐27 and IL‐12, and down‐regulates IL‐23 and IL‐1beta in dendritic cells (DCs), establishing inhibitory conditions for Th‐17 cell differentiation: Implications for treatment of multiple sclerosis (MS)
Ramgolam V, Speer D, Markovic‐Plese S. Interferon (IFN) beta ‐1a induces IL‐27 and IL‐12, and down‐regulates IL‐23 and IL‐1beta in dendritic cells (DCs), establishing inhibitory conditions for Th‐17 cell differentiation: Implications for treatment of multiple sclerosis (MS). The FASEB Journal 2008, 22: 1074.8-1074.8. DOI: 10.1096/fasebj.22.1_supplement.1074.8.Peer-Reviewed Original ResearchIFN beta-1aDendritic cellsIL-27Beta-1aMultiple sclerosisIL-23IL-1 betaIL-1betaPathogenesis of MSIL-23 promotesIL-27 expressionTh-17 cellsMature dendritic cellsInterferon beta-1aIL-1B expressionCytokines IL-6Cytokine gene expressionInduction of SOCS3Cell differentiationSTAT-1 activationExpression of SOCS3STAT-1 geneQuantitative RT-PCRMS patientsStandard therapy