PI3Kγ deficiency delays the onset of experimental autoimmune encephalomyelitis and ameliorates its clinical outcome.

2.50
Hdl Handle:
http://hdl.handle.net/10033/346208
Title:
PI3Kγ deficiency delays the onset of experimental autoimmune encephalomyelitis and ameliorates its clinical outcome.
Authors:
Berod, Luciana; Heinemann, Christina; Heink, Sylvia; Escher, Angelika; Stadelmann, Christine; Drube, Sebastian; Wetzker, Reinhard; Norgauer, Johannes; Kamradt, Thomas
Abstract:
PI3Ks control signal transduction triggered by growth factors and G-protein-coupled receptors and regulate an array of biological processes, including cellular proliferation, differentiation, survival and migration. Herein, we investigated the role of PI3Kγ in the pathogenesis of EAE. We show that, in the absence of PI3Kγ expression, clinical signs of EAE were delayed and mitigated. PI3Kγ-deficient myelin oligodendrocyte glycoprotein (MOG)(35-55) -specific CD4(+) T cells appeared later in the secondary lymphoid organs and in the CNS than their WT counterparts. Transfer of WT CD4(+) cells into PI3Kγ(-/-) mice prior to MOG(35-55) immunisation restored EAE severity to WT levels, supporting the relevance of PI3Kγ expression in Th cells for the pathogenesis of EAE; however, PI3Kγ was dispensable for Th1 and Th17 differentiation, thus excluding an altered expression of these pathogenetically relevant cytokines as the cause for ameliorated EAE in PI3Kγ(-/-) mice. These findings demonstrate that PI3Kγ contributes to the development of autoimmune CNS inflammation.
Citation:
PI3Kγ deficiency delays the onset of experimental autoimmune encephalomyelitis and ameliorates its clinical outcome. 2011, 41 (3):833-44 Eur. J. Immunol.
Journal:
European journal of immunology
Issue Date:
Mar-2011
URI:
http://hdl.handle.net/10033/346208
DOI:
10.1002/eji.201040504
PubMed ID:
21287545
Type:
Article
Language:
en
ISSN:
1521-4141
Appears in Collections:
publications of the research group intravital microscopy in infection and immunity (INMI)

Full metadata record

DC FieldValue Language
dc.contributor.authorBerod, Lucianaen
dc.contributor.authorHeinemann, Christinaen
dc.contributor.authorHeink, Sylviaen
dc.contributor.authorEscher, Angelikaen
dc.contributor.authorStadelmann, Christineen
dc.contributor.authorDrube, Sebastianen
dc.contributor.authorWetzker, Reinharden
dc.contributor.authorNorgauer, Johannesen
dc.contributor.authorKamradt, Thomasen
dc.date.accessioned2015-03-05T12:32:37Zen
dc.date.available2015-03-05T12:32:37Zen
dc.date.issued2011-03en
dc.identifier.citationPI3Kγ deficiency delays the onset of experimental autoimmune encephalomyelitis and ameliorates its clinical outcome. 2011, 41 (3):833-44 Eur. J. Immunol.en
dc.identifier.issn1521-4141en
dc.identifier.pmid21287545en
dc.identifier.doi10.1002/eji.201040504en
dc.identifier.urihttp://hdl.handle.net/10033/346208en
dc.description.abstractPI3Ks control signal transduction triggered by growth factors and G-protein-coupled receptors and regulate an array of biological processes, including cellular proliferation, differentiation, survival and migration. Herein, we investigated the role of PI3Kγ in the pathogenesis of EAE. We show that, in the absence of PI3Kγ expression, clinical signs of EAE were delayed and mitigated. PI3Kγ-deficient myelin oligodendrocyte glycoprotein (MOG)(35-55) -specific CD4(+) T cells appeared later in the secondary lymphoid organs and in the CNS than their WT counterparts. Transfer of WT CD4(+) cells into PI3Kγ(-/-) mice prior to MOG(35-55) immunisation restored EAE severity to WT levels, supporting the relevance of PI3Kγ expression in Th cells for the pathogenesis of EAE; however, PI3Kγ was dispensable for Th1 and Th17 differentiation, thus excluding an altered expression of these pathogenetically relevant cytokines as the cause for ameliorated EAE in PI3Kγ(-/-) mice. These findings demonstrate that PI3Kγ contributes to the development of autoimmune CNS inflammation.en
dc.language.isoenen
dc.subject.meshAdoptive Transferen
dc.subject.meshAnimalsen
dc.subject.meshCell Differentiationen
dc.subject.meshClass Ib Phosphatidylinositol 3-Kinaseen
dc.subject.meshEncephalomyelitis, Autoimmune, Experimentalen
dc.subject.meshGlycoproteinsen
dc.subject.meshLymphoid Tissueen
dc.subject.meshMiceen
dc.subject.meshMice, Inbred C57BLen
dc.subject.meshMice, Knockouten
dc.subject.meshMyelin-Oligodendrocyte Glycoproteinen
dc.subject.meshPeptide Fragmentsen
dc.subject.meshT-Lymphocytes, Helper-Induceren
dc.subject.meshTime Factorsen
dc.titlePI3Kγ deficiency delays the onset of experimental autoimmune encephalomyelitis and ameliorates its clinical outcome.en
dc.typeArticleen
dc.identifier.journalEuropean journal of immunologyen

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