Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-7577
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dc.contributor.authorWeber, Michael-
dc.contributor.authorLupp, Corinna-
dc.contributor.authorStein, Pamela-
dc.contributor.authorKreft, Andreas-
dc.contributor.authorBopp, Tobias-
dc.contributor.authorWehler, Thomas-
dc.contributor.authorSchmitt, Edgar-
dc.contributor.authorSchild, Hansjörg-
dc.contributor.authorRadsak, Markus-
dc.date.accessioned2022-08-19T08:45:55Z-
dc.date.available2022-08-19T08:45:55Z-
dc.date.issued2013-
dc.identifier.urihttps://openscience.ub.uni-mainz.de/handle/20.500.12030/7591-
dc.description.abstractGraft-versus-host disease (GvHD) is a key contributor to the morbidity and mortality after allogeneic hematopoetic stem cell transplantation (HSCT). Regulatory Foxp3(+) CD4(+) T cells (Treg) suppress conventional T cell activation and can control GvHD. In our previous work, we demonstrate that a basic mechanism of Treg mediated suppression occurs by the transfer of cyclic adenosine monophosphate (cAMP) to responder cells. Whether this mechanism is relevant for Treg mediated suppression of GvHD is currently unknown. To address this question, bone marrow and T cells from C57BL/6 mice were transferred into lethally irradiated BALB/c recipients, and the course of GvHD and survival were monitored. Transplanted recipients developed severe GvHD that was strongly ameliorated by the transfer of donor Treg cells. Towards the underlying mechanisms, in vitro studies revealed that Treg communicated with DCs via gap junctions, resulting in functional inactivation of DC by a metabolic pathway involving cAMP that is modulated by the phosphodiesterase (PDE) 4 inhibitor rolipram. PDE2 or PDE3 inhibitors as well as rolipram suppressed allogeneic T cell activation, indirectly by enhancing Treg mediated suppression of DC activation and directly by inhibiting responder T cell proliferation. In line with this, we observed a cooperative suppression of GvHD upon Treg transfer and additional rolipram treatment. In conclusion, we propose that an important pathway of Treg mediated control of GvHD is based on a cAMP dependent mechanism. These data provide the basis for future concepts to manipulate allogeneic T cell responses to prevent GvHD.en_GB
dc.description.sponsorshipDFG, Open Access-Publizieren Universität Mainz / Universitätsmedizinde
dc.language.isoengde
dc.rightsCC BY*
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/*
dc.subject.ddc610 Medizinde_DE
dc.subject.ddc610 Medical sciencesen_GB
dc.titleMechanisms of Cyclic Nucleotide Phosphodiesterases in Modulating T Cell Responses in Murine Graft-versus-Host Diseaseen_GB
dc.typeZeitschriftenaufsatzde
dc.identifier.doihttp://doi.org/10.25358/openscience-7577-
jgu.type.dinitypearticleen_GB
jgu.type.versionPublished versionde
jgu.type.resourceTextde
jgu.organisation.departmentFB 04 Medizinde
jgu.organisation.number2700-
jgu.organisation.nameJohannes Gutenberg-Universität Mainz-
jgu.rights.accessrightsopenAccess-
jgu.journal.titlePLoS onede
jgu.journal.volume8de
jgu.journal.issue3de
jgu.pages.alternativee58110de
jgu.publisher.year2013-
jgu.publisher.namePLoSde
jgu.publisher.placeLawrence, Kan.de
jgu.publisher.urihttp://dx.doi.org/10.1371/journal.pone.0058110de
jgu.publisher.issn1932-6203de
jgu.organisation.placeMainz-
jgu.identifier.pmid23483980-
jgu.subject.ddccode610de
opus.date.modified2018-08-02T09:40:57Z-
opus.subject.dfgcode04-205-
opus.organisation.stringFB 04: Medizin: Institut für Immunologiede_DE
opus.organisation.stringFB 04: Medizin: Institut für Pathologiede_DE
opus.organisation.stringFB 04: Medizin: III. Medizinische Klinik und Poliklinikde_DE
opus.identifier.opusid22889-
opus.importsourcepubmed-
opus.institute.number0412-
opus.institute.number0423-
opus.institute.number0427-
opus.metadataonlyfalse-
opus.type.contenttypeKeinede_DE
opus.type.contenttypeNoneen_EN
opus.affiliatedKreft, Andreas-
opus.affiliatedBopp, Tobias-
opus.affiliatedWehler, Thomas-
opus.affiliatedSchmitt, Edgar-
opus.affiliatedSchild, Hansjörg-
opus.affiliatedRadsak, Markus-
jgu.publisher.doi10.1371/journal.pone.0058110de
jgu.organisation.rorhttps://ror.org/023b0x485-
Appears in collections:DFG-OA-Publizieren (2012 - 2017)

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