Weber, Martin S.

[["dc.bibliographiccitation.artnumber","e20"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Neurology® neuroimmunology & neuroinflammation"],["dc.bibliographiccitation.volume","1"],["dc.contributor.author","Varrin-Doyer, Michel"],["dc.contributor.author","Shetty, Aparna"],["dc.contributor.author","Spencer, Collin M."],["dc.contributor.author","Schulze-Topphoff, Ulf"],["dc.contributor.author","Weber, Martin S."],["dc.contributor.author","Bernard, Claude C. A."],["dc.contributor.author","Forsthuber, Thomas"],["dc.contributor.author","Cree, Bruce A. C."],["dc.contributor.author","Slavin, Anthony J."],["dc.contributor.author","Zamvil, Scott S."],["dc.date.accessioned","2015-10-20T13:25:31Z"],["dc.date.accessioned","2021-10-27T13:20:19Z"],["dc.date.available","2015-10-20T13:25:31Z"],["dc.date.available","2021-10-27T13:20:19Z"],["dc.date.issued","2014-08-01"],["dc.description.abstract","OBJECTIVE: Recently, we reported that the 218 amino acid murine full-length myelin oligodendrocyte glycoprotein (MOG) contains novel T-cell epitopes p119-132, p181-195, and p186-200, located within its transmembrane and cytoplasmic domains, and that p119-132 is its immunodominant encephalitogenic T-cell epitope in mice. Here, we investigated whether the corresponding human MOG sequences contain T-cell epitopes in patients with multiple sclerosis (MS) and healthy controls (HC). METHODS: Peripheral blood T cells from patients with MS and HC were examined for proliferation to MOG p119-130, p181-195, p186-200, and p35-55 by fluorescence-activated cell sorting analysis using carboxylfluorescein diacetate succinimidyl ester dilution assay. Intracellular production of proinflammatory cytokines was analyzed by flow cytometry. RESULTS: MOG p119-130, p181-195, and p186-200 elicited significantly greater T-cell responses than p35-55 in patients with MS. T cells from patients with MS proliferated significantly more strongly to MOG p119-130 and p186-200 than did T cells from HC. Further, MOG p119-130-specific T cells exhibited Th17 polarization, suggesting this T-cell epitope may be relevant to MS pathogenesis. CONCLUSIONS: Transmembrane and cytoplasmic MOG domains contain potent T-cell epitopes in MS. Recognition of these determinants is important when evaluating T-cell responses to MOG in MS and may have implications for development of myelin antigen-based therapeutics."],["dc.identifier.doi","10.1212/NXI.0000000000000020"],["dc.identifier.fs","611981"],["dc.identifier.pmid","25340072"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12194"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/91955"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.relation.issn","2332-7812"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","CC BY-NC-ND 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/3.0"],["dc.title","MOG transmembrane and cytoplasmic domains contain highly stimulatory T-cell epitopes in MS."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","e698"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Neurology - Neuroimmunology Neuroinflammation"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Häusler, Darius"],["dc.contributor.author","Hajiyeva, Zivar"],["dc.contributor.author","Traub, Jan W."],["dc.contributor.author","Zamvil, Scott S."],["dc.contributor.author","Lalive, Patrice H."],["dc.contributor.author","Brück, Wolfgang"],["dc.contributor.author","Weber, Martin S."],["dc.date.accessioned","2021-04-14T08:26:30Z"],["dc.date.available","2021-04-14T08:26:30Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1212/NXI.0000000000000698"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/81971"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","2332-7812"],["dc.title","Glatiramer acetate immune modulates B-cell antigen presentation in treatment of MS"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e179"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Neurology® neuroimmunology & neuroinflammation"],["dc.bibliographiccitation.volume","2"],["dc.contributor.author","Molnarfi, Nicolas"],["dc.contributor.author","Prod'homme, Thomas"],["dc.contributor.author","Schulze-Topphoff, Ulf"],["dc.contributor.author","Spencer, Collin M."],["dc.contributor.author","Weber, Martin S."],["dc.contributor.author","Patarroyo, Juan C."],["dc.contributor.author","Lalive, Patrice H."],["dc.contributor.author","Zamvil, Scott S."],["dc.date.accessioned","2016-08-23T06:34:34Z"],["dc.date.accessioned","2021-10-27T13:20:40Z"],["dc.date.available","2016-08-23T06:34:34Z"],["dc.date.available","2021-10-27T13:20:40Z"],["dc.date.issued","2015-12-01"],["dc.description.abstract","OBJECTIVE: Glatiramer acetate (GA; Copaxone), a disease-modifying therapy for multiple sclerosis (MS), promotes development of anti-inflammatory (M2, type II) monocytes that can direct differentiation of regulatory T cells. We investigated the innate immune signaling pathways that participate in GA-mediated M2 monocyte polarization. METHODS: Monocytes were isolated from myeloid differentiation primary response gene 88 (MyD88)-deficient, Toll-IL-1 receptor domain-containing adaptor inducing interferon (IFN)-β (TRIF)-deficient, IFN-α/β receptor subunit 1 (IFNAR1)-deficient, and wild-type (WT) mice and human peripheral blood. GA-treated monocytes were stimulated with Toll-like receptor ligands, then evaluated for activation of kinases and transcription factors involved in innate immunity, and secretion of proinflammatory cytokines. GA-treated mice were evaluated for cytokine secretion and susceptibility to experimental autoimmune encephalomyelitis. RESULTS: GA-mediated inhibition of proinflammatory cytokine production by monocytes occurred independently of MyD88 and nuclear factor-κB, but was blocked by TRIF deficiency. Furthermore, GA did not provide clinical benefit in TRIF-deficient mice. GA inhibited activation of p38 mitogen-activated protein kinase, an upstream regulator of activating transcription factor (ATF)-2, and c-Jun N-terminal kinase 1, which regulates IFN regulatory factor 3 (IRF3). Consequently, nuclear translocation of ATF-2 and IRF3, components of the IFN-β enhanceosome, was impaired. Consistent with these observations, GA inhibited production of IFN-β in vivo in WT mice, but did not modulate proinflammatory cytokine production by monocytes from IFNAR1-deficient mice. CONCLUSION: Our results demonstrate that GA inhibits the type I IFN pathway in M2 polarization of monocytes independently of MyD88, providing an important mechanism connecting innate and adaptive immune modulation in GA therapy and valuable insight regarding its potential use with other MS treatments."],["dc.identifier.doi","10.1212/NXI.0000000000000179"],["dc.identifier.fs","619056"],["dc.identifier.pmid","26601118"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13593"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/91975"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.relation.issn","2332-7812"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0"],["dc.title","Glatiramer acetate treatment negatively regulates type I interferon signaling."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","7"],["dc.bibliographiccitation.issue","1-2"],["dc.bibliographiccitation.journal","Journal of Neuroimmunology"],["dc.bibliographiccitation.lastpage","8"],["dc.bibliographiccitation.volume","275"],["dc.contributor.author","Kinzel, Silke"],["dc.contributor.author","Lehmann-Horn, Klaus"],["dc.contributor.author","Zamvil, Scott S."],["dc.contributor.author","Winkler, Anne"],["dc.contributor.author","Bernard, Claude C."],["dc.contributor.author","Stadelmann-Nessler, Christine"],["dc.contributor.author","Brueck, Wolfgang"],["dc.contributor.author","Weber, Martin S."],["dc.date.accessioned","2018-11-07T09:33:33Z"],["dc.date.available","2018-11-07T09:33:33Z"],["dc.date.issued","2014"],["dc.identifier.doi","10.1016/j.jneuroim.2014.08.026"],["dc.identifier.isi","000345192100019"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/31990"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.publisher.place","Amsterdam"],["dc.relation.eventlocation","Mainz, GERMANY"],["dc.relation.issn","1872-8421"],["dc.relation.issn","0165-5728"],["dc.title","Myelin-specific antibodies trigger spontaneous CNS autoimmune disease in the absence of myelin-specific B cells"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","9773"],["dc.bibliographiccitation.issue","39"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences"],["dc.bibliographiccitation.lastpage","9778"],["dc.bibliographiccitation.volume","115"],["dc.contributor.author","Häusler, Darius"],["dc.contributor.author","Häusser-Kinzel, Silke"],["dc.contributor.author","Feldmann, Linda"],["dc.contributor.author","Torke, Sebastian"],["dc.contributor.author","Lepennetier, Gildas"],["dc.contributor.author","Bernard, Claude C. A."],["dc.contributor.author","Zamvil, Scott S."],["dc.contributor.author","Brück, Wolfgang"],["dc.contributor.author","Lehmann-Horn, Klaus"],["dc.contributor.author","Weber, Martin S."],["dc.date.accessioned","2021-06-01T10:51:05Z"],["dc.date.available","2021-06-01T10:51:05Z"],["dc.date.issued","2018"],["dc.description.abstract","The anti-CD20 antibody ocrelizumab, approved for treatment of multiple sclerosis, leads to rapid elimination of B cells from the blood. The extent of B cell depletion and kinetics of their recovery in different immune compartments is largely unknown. Here, we studied how anti-CD20 treatment influences B cells in bone marrow, blood, lymph nodes, and spleen in models of experimental autoimmune encephalomyelitis (EAE). Anti-CD20 reduced mature B cells in all compartments examined, although a subpopulation of antigen-experienced B cells persisted in splenic follicles. Upon treatment cessation, CD20 + B cells simultaneously repopulated in bone marrow and spleen before their reappearance in blood. In EAE induced by native myelin oligodendrocyte glycoprotein (MOG), a model in which B cells are activated, B cell recovery was characterized by expansion of mature, differentiated cells containing a high frequency of myelin-reactive B cells with restricted B cell receptor gene diversity. Those B cells served as efficient antigen-presenting cells (APCs) for activation of myelin-specific T cells. In MOG peptide-induced EAE, a purely T cell-mediated model that does not require B cells, in contrast, reconstituting B cells exhibited a naive phenotype without efficient APC capacity. Our results demonstrate that distinct subpopulations of B cells differ in their sensitivity to anti-CD20 treatment and suggest that differentiated B cells persisting in secondary lymphoid organs contribute to the recovering B cell pool."],["dc.identifier.doi","10.1073/pnas.1810470115"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/86889"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation.eissn","1091-6490"],["dc.relation.issn","0027-8424"],["dc.title","Functional characterization of reappearing B cells after anti-CD20 treatment of CNS autoimmune disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e22"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Neurology® neuroimmunology & neuroinflammation"],["dc.bibliographiccitation.volume","1"],["dc.contributor.author","Shetty, Aparna"],["dc.contributor.author","Gupta, Sheena G."],["dc.contributor.author","Varrin-Doyer, Michel"],["dc.contributor.author","Weber, Martin S."],["dc.contributor.author","Prod'homme, Thomas"],["dc.contributor.author","Molnarfi, Nicolas"],["dc.contributor.author","Ji, Niannian"],["dc.contributor.author","Nelson, Patricia A."],["dc.contributor.author","Patarroyo, Juan C."],["dc.contributor.author","Schulze-Topphoff, Ulf"],["dc.contributor.author","Fogal, Stephen E."],["dc.contributor.author","Forsthuber, Thomas"],["dc.contributor.author","Sobel, Raymond A."],["dc.contributor.author","Bernard, Claude C. A."],["dc.contributor.author","Slavin, Anthony J."],["dc.contributor.author","Zamvil, Scott S."],["dc.date.accessioned","2015-10-20T13:30:20Z"],["dc.date.accessioned","2021-10-27T13:20:19Z"],["dc.date.available","2015-10-20T13:30:20Z"],["dc.date.available","2021-10-27T13:20:19Z"],["dc.date.issued","2014-08-01"],["dc.description.abstract","OBJECTIVE: Studies evaluating T-cell recognition of myelin oligodendrocyte glycoprotein (MOG) in multiple sclerosis (MS) and its model, experimental autoimmune encephalomyelitis (EAE), have focused mostly on its 117 amino acid (aa) extracellular domain, especially peptide (p) 35-55. We characterized T-cell responses to the entire 218 aa MOG sequence, including its transmembrane and cytoplasmic domains. METHODS: T-cell recognition in mice was examined using overlapping peptides and intact full-length mouse MOG. EAE was evaluated by peptide immunization and by adoptive transfer of MOG epitope-specific T cells. Frequency of epitope-specific T cells was examined by ELISPOT. RESULTS: Three T-cell determinants of MOG were discovered in its transmembrane and cytoplasmic domains, p119-132, p181-195, and p186-200. Transmembrane MOG p119-132 induced clinical EAE, CNS inflammation, and demyelination as potently as p35-55 in C57BL/6 mice and other H-2(b) strains. p119-128 contained its minimal encephalitogenic epitope. p119-132 did not cause disease in EAE-susceptible non-H-2(b) strains, including Biozzi, NOD, and PL/J. MOG p119-132-specific T cells produced Th1 and Th17 cytokines and transferred EAE to wild-type recipient mice. After immunization with full-length MOG, a significantly higher frequency of MOG-reactive T cells responded to p119-132 than to p35-55, demonstrating that p119-132 is an immunodominant encephalitogenic epitope. MOG p181-195 did not cause EAE, and MOG p181-195-specific T cells could not transfer EAE into wild-type or highly susceptible T- and B-cell-deficient mice. CONCLUSIONS: Transmembrane and cytoplasmic domains of MOG contain immunodominant T-cell epitopes in EAE. A CNS autoantigen can also contain nonpathogenic stimulatory T-cell epitopes. Recognition that a myelin antigen contains multiple encephalitogenic and nonencephalitogenic determinants may have implications for therapeutic development in MS."],["dc.identifier.doi","10.1212/NXI.0000000000000022"],["dc.identifier.fs","611980"],["dc.identifier.pmid","25340074"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12195"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/91956"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.relation.issn","2332-7812"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","CC BY-NC-ND 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/3.0"],["dc.title","Immunodominant T-cell epitopes of MOG reside in its transmembrane and cytoplasmic domains in EAE."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","67"],["dc.bibliographiccitation.journal","Journal of Neuroinflammation"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Cravens, Petra D."],["dc.contributor.author","Kieseier, Bernd C."],["dc.contributor.author","Hussain, Rehana Z."],["dc.contributor.author","Herndon, Emily"],["dc.contributor.author","Arellano, Benjamine"],["dc.contributor.author","Ben, Li-Hong"],["dc.contributor.author","Timmons, Brenda C."],["dc.contributor.author","Castro-Rojas, Cyd"],["dc.contributor.author","Hartung, Hans-Peter"],["dc.contributor.author","Hemmer, Bernhard"],["dc.contributor.author","Weber, Martin S."],["dc.contributor.author","Zamvil, Scott S."],["dc.contributor.author","Stueve, Olaf"],["dc.date.accessioned","2018-11-07T09:24:35Z"],["dc.date.available","2018-11-07T09:24:35Z"],["dc.date.issued","2013"],["dc.description.abstract","Multiple sclerosis (MS) is thought to be a CD4(+) T cell mediated autoimmune demyelinating disease of the central nervous system (CNS) that is rarely diagnosed during infancy. Cellular and molecular mechanisms that confer disease resistance in this age group are unknown. We tested the hypothesis that a differential composition of immune cells within the CNS modulates age- associated susceptibility to CNS autoimmune disease. C57BL/6 mice younger than eight weeks were resistant to experimental autoimmune encephalomyelitis (EAE) following active immunization with myelin oligodendrocyte glycoprotein (MOG) peptide (p) 35-55. Neonates also developed milder EAE after transfer of adult encephalitogenic T cells primed by adult or neonate antigen presenting cells (APC). There was a significant increase in CD45(+) hematopoietic immune cells and CD45(+) high side scatter granulocytes in the CNS of adults, but not in neonates. Within the CD45(+) immune cell compartment of adults, the accumulation of CD4(+) T cells, Gr-1(+) and Gr-1(-) monocytes and CD11c(+) dendritic cells (DC) was identified. A significantly greater percentage of CD19(+) B cells in the adult CNS expressed MHC II than neonate CNS B cells. Only in the adult CNS could IFN gamma transcripts be detected 10 days post immunization for EAE. IFN gamma is highly expressed by adult donor CD4(+) T cells that are adoptively transferred but not by transferred neonate donor cells. In contrast, IL-17 transcripts could not be detected in adult or neonate CNS in this EAE model, and neither adult nor neonate donor CD4(+) T cells expressed IL-17 at the time of adoptive transfer."],["dc.identifier.doi","10.1186/1742-2094-10-67"],["dc.identifier.isi","000320058000001"],["dc.identifier.pmid","23705890"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/9105"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29863"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1742-2094"],["dc.rights","CC BY 2.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.0"],["dc.title","The neonatal CNS is not conducive for encephalitogenic Th1 T cells and B cells during experimental autoimmune encephalomyelitis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","29"],["dc.bibliographiccitation.journal","Journal of Neuroinflammation"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Weber, Martin S."],["dc.contributor.author","Prod'homme, Thomas"],["dc.contributor.author","Youssef, Sawsan"],["dc.contributor.author","Dunn, Shannon E."],["dc.contributor.author","Steinman, Lawrence"],["dc.contributor.author","Zamvil, Scott S."],["dc.date.accessioned","2018-11-07T09:43:50Z"],["dc.date.available","2018-11-07T09:43:50Z"],["dc.date.issued","2014"],["dc.description.abstract","Oral atorvastatin has prevented or reversed paralysis in the multiple sclerosis (MS) model experimental autoimmune encephalomyelitis (EAE), and reduced development of new MS lesions in clinical trials. Besides inhibiting development of encephalitogenic T cells, atorvastatin treatment of EAE has been associated with an induction of anti-inflammatory myelin-reactive T-helper type (Th)-2 cells. To investigate the clinical significance of atorvastatin-mediated Th2 differentiation, we first evaluated atorvastatin treatment in interleukin (IL)-4 green fluorescent protein-enhanced transcript (4-GET) reporter mice. Atorvastatin treatment failed to induce IL-4-producing Th2 cells in vivo; however, when T cells from atorvastatin-treated 4-GET mice were reactivated in vitro, T cells preferentially differentiated into Th2 cells, while antigen-specific T-cell proliferation and secretion of proinflammatory cytokines (interferon gamma, IL-17, tumor necrosis factor and IL-12) were reduced. Oral atorvastatin also prevented or reversed EAE in signal transducer and activator of transcription 6-deficient (STAT6(-/-)) mice, which cannot generate IL-4-producing Th2 cells. Further, atorvastatin treatment did not induce or expand Foxp3(+) regulatory T cells in either wild-type or STAT6(-/-) mice. In vivo proliferation of T cells, as measured by incorporation of bromodeoxyuridine, was inhibited in atorvastatin-treated wild-type and STAT6(-/-) mice. These data imply that atorvastatin ameliorates central nervous system autoimmune disease primarily by inhibiting proliferation of proinflammatory encephalitogenic T cells, and not simply through induction of anti-inflammatory Th2 cells. This cytostatic effect may be a relevant mechanism of action when considering use of statins in MS and other inflammatory conditions."],["dc.description.sponsorship","NIAID NIH HHS [R01 AI059709]"],["dc.identifier.doi","10.1186/1742-2094-11-29"],["dc.identifier.isi","000333237900001"],["dc.identifier.pmid","24498870"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10055"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/34265"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1742-2094"],["dc.rights","CC BY 2.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.0"],["dc.title","Neither T-helper type 2 nor Foxp3(+) regulatory T cells are necessary for therapeutic benefit of atorvastatin in treatment of central nervous system autoimmunity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2078"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","European Journal of Immunology"],["dc.bibliographiccitation.lastpage","2088"],["dc.bibliographiccitation.volume","43"],["dc.contributor.author","Hertzenberg, Deetje"],["dc.contributor.author","Lehmann-Horn, Klaus"],["dc.contributor.author","Kinzel, Silke"],["dc.contributor.author","Husterer, Veronika"],["dc.contributor.author","Cravens, Petra D."],["dc.contributor.author","Kieseier, Bernd C."],["dc.contributor.author","Hemmer, Bernhard"],["dc.contributor.author","Brueck, Wolfgang"],["dc.contributor.author","Zamvil, Scott S."],["dc.contributor.author","Stueve, Olaf"],["dc.contributor.author","Weber, Martin S."],["dc.date.accessioned","2018-11-07T09:21:31Z"],["dc.date.available","2018-11-07T09:21:31Z"],["dc.date.issued","2013"],["dc.description.abstract","MS is an inflammatory CNS disorder, which typically occurs in early adulthood and rarely in children. Here we tested whether functional maturation of innate immune cells may determine susceptibility to CNS autoimmune disease in EAE. Two-week-old mice were resistant to active EAE, which causes fulminant paralysis in adult mice; this resistance was associated with an impaired development of Th1 and Th17 cells. Resistant, young mice had higher frequencies of myeloid-derived suppressor cells and plasma-cytoid DCs. Furthermore, myeloid APCs and B cells from young mice expressed lower levels of MHC class II and CD40, produced decreased amounts of proinflammatory cytokines, and released enhanced levels of anti-inflammatory IL-10. When used as APCs, splenocytes from 2-week-old mice failed to differentiate naive T cells into Th1 and Th17 cells irrespective of the T-cell donor's age, and promoted development of Treg cells and Th2 cells instead. Adoptive transfer of adult APCs restored the ability of 2-week-old mice to generate encephalitogenic T cells and develop EAE. Collectively, these findings indicate that the innate immune compartment functionally matures during development, which may be a prerequisite for development of T-cell-mediated CNS autoimmune disease."],["dc.identifier.doi","10.1002/eji.201343338"],["dc.identifier.isi","000328839700012"],["dc.identifier.pmid","23637087"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29126"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1521-4141"],["dc.relation.issn","0014-2980"],["dc.title","Developmental maturation of innate immune cell function correlates with susceptibility to central nervous system autoimmunity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1315"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","JAMA Neurology"],["dc.bibliographiccitation.lastpage","1324"],["dc.bibliographiccitation.volume","70"],["dc.contributor.author","Brueck, Wolfgang"],["dc.contributor.author","Gold, Ralf"],["dc.contributor.author","Lund, Brett T."],["dc.contributor.author","Oreja-Guevara, Celia"],["dc.contributor.author","Prat, Alexandre"],["dc.contributor.author","Spencer, Collin M."],["dc.contributor.author","Steinman, Lawrence"],["dc.contributor.author","Tintore, Mar"],["dc.contributor.author","Vollmer, Timothy L."],["dc.contributor.author","Weber, Martin S."],["dc.contributor.author","Weiner, Leslie P."],["dc.contributor.author","Ziemssen, Tjalf"],["dc.contributor.author","Zamvil, Scott S."],["dc.date.accessioned","2018-11-07T09:18:49Z"],["dc.date.available","2018-11-07T09:18:49Z"],["dc.date.issued","2013"],["dc.description.abstract","Several innovative disease-modifying treatments (DMTs) for relapsing-remitting multiple sclerosis have been licensed recently or are in late-stage development. The molecular targets of several of these DMTs are well defined. All affect at least 1 of 4 properties, namely (1) trafficking, (2) survival, (3) function, or (4) proliferation. In contrast to beta-interferons and glatiramer acetate, the first-generation DMTs, several newer therapies are imbued with safety issues, which may be attributed to their structure or metabolism. In addition to efficacy, understanding the relationship between the mechanism of action of the DMTs and their safety profile is pertinent for decision making and patient care. In this article, we focus primarily on the safety of DMTs in the context of understanding their pharmacological characteristics, including molecular targets, mechanism of action, chemical structure, and metabolism. While understanding mechanisms underlying DMT toxicities is incomplete, it is important to further develop this knowledge to minimize risk to patients and to ensure future therapies have the most advantageous benefit-risk profiles. Recognizing the individual classes of DMTs described here may be valuable when considering use of such agents sequentially or possibly in combination."],["dc.description.sponsorship","Teva Pharmaceuticals Inc."],["dc.identifier.doi","10.1001/jamaneurol.2013.3510"],["dc.identifier.isi","000330114400017"],["dc.identifier.pmid","23921521"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/28487"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Medical Assoc"],["dc.relation.issn","2168-6157"],["dc.relation.issn","2168-6149"],["dc.title","Therapeutic Decisions in Multiple Sclerosis Moving Beyond Efficacy"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]