Please use this identifier to cite or link to this item:
http://doi.org/10.25358/openscience-7927Full metadata record
| DC Field | Value | Language |
|---|---|---|
| dc.contributor.author | Trinschek, Bettina | - |
| dc.contributor.author | Lüssi, Felix | - |
| dc.contributor.author | Haas, Jürgen | - |
| dc.contributor.author | Wildemann, Brigitte | - |
| dc.contributor.author | Zipp, Frauke | - |
| dc.contributor.author | Wiendl, Heinz | - |
| dc.contributor.author | Becker, Christian | - |
| dc.contributor.author | Jonuleit, Helmut | - |
| dc.date.accessioned | 2022-10-10T08:22:53Z | - |
| dc.date.available | 2022-10-10T08:22:53Z | - |
| dc.date.issued | 2013 | - |
| dc.identifier.uri | https://openscience.ub.uni-mainz.de/handle/20.500.12030/7942 | - |
| dc.description.abstract | In multiple sclerosis (MS) autoaggressive T effector cells (Teff) are not efficiently controlled by regulatory T cells (Treg) but the underlying mechanisms are incompletely understood. Proinflammatory cytokines are key factors facilitating Teff activity in chronic inflammation. Here we investigated the influence of IL-6 on Treg sensitivity of Teff from therapy-naïve MS patients with or without active disease. Compared to healthy volunteers and independent of disease course CD4 and especially CD8 MS-Teff were insensitive against functional active Treg from healthy controls. This unresponsiveness was caused by accelerated production of IL-6, elevated IL-6 receptor expression and phosphorylation of protein kinase B (PKB)/c-Akt in MS-Teff. In a positive feedback loop, IL-6 itself induced its accelerated synthesis and enhanced phosphorylation of PKB/c-Akt that finally mediated Treg resistance. Furthermore, accelerated IL-6 release especially by CD8 Teff prevented control of surrounding Teff, described here as bystander resistance . Blockade of IL-6 receptor signaling or direct inhibition of PKB/c-Akt phosphorylation restored Treg responsiveness of Teff and prevented bystander resistance. In Teff of healthy controls (HC) exogenous IL-6 also changed the kinetics of IL-6 production and induced Treg unresponsiveness. This modulation was only transient in Teff from healthy volunteers, whereas accelerated IL-6 production in MS-Teff maintained also in absence of IL-6. Hence, we showed that the kinetics of IL-6 production instead of elevated IL-6 levels defines the Teff responsiveness in early Treg-T cell communication in MS independent of their disease course and propose IL-6 and associated PKB/c-Akt activation as effective therapeutic targets for modulation of Teff activity in MS. | en_GB |
| dc.description.sponsorship | DFG, Open Access-Publizieren Universität Mainz / Universitätsmedizin | de |
| dc.language.iso | eng | de |
| dc.rights | CC BY | * |
| dc.rights.uri | https://creativecommons.org/licenses/by/3.0/ | * |
| dc.subject.ddc | 610 Medizin | de_DE |
| dc.subject.ddc | 610 Medical sciences | en_GB |
| dc.title | Kinetics of IL-6 production defines T effector cell responsiveness to regulatory T cells in multiple sclerosis | en_GB |
| dc.type | Zeitschriftenaufsatz | de |
| dc.identifier.doi | http://doi.org/10.25358/openscience-7927 | - |
| jgu.type.dinitype | article | en_GB |
| jgu.type.version | Published version | de |
| jgu.type.resource | Text | de |
| jgu.organisation.department | FB 04 Medizin | de |
| jgu.organisation.number | 2700 | - |
| jgu.organisation.name | Johannes Gutenberg-Universität Mainz | - |
| jgu.rights.accessrights | openAccess | - |
| jgu.journal.title | Plos one | de |
| jgu.journal.volume | 8 | de |
| jgu.journal.issue | 10 | de |
| jgu.pages.alternative | e77634 | de |
| jgu.publisher.year | 2013 | - |
| jgu.publisher.name | PLoS | de |
| jgu.publisher.place | Lawrence, Kan. | de |
| jgu.publisher.uri | http://dx.doi.org/10.1371/journal.pone.0077634 | de |
| jgu.publisher.issn | 1932-6203 | de |
| jgu.organisation.place | Mainz | - |
| jgu.subject.ddccode | 610 | de |
| opus.date.modified | 2018-08-02T09:35:55Z | - |
| opus.subject.dfgcode | 04-204 | - |
| opus.organisation.string | FB 04: Medizin: Hautklinik | de_DE |
| opus.organisation.string | FB 04: Medizin: Klinik und Poliklinik für Neurologie | de_DE |
| opus.identifier.opusid | 24289 | - |
| opus.institute.number | 0431 | - |
| opus.institute.number | 0435 | - |
| opus.metadataonly | false | - |
| opus.type.contenttype | Forschungsbericht | de_DE |
| opus.type.contenttype | Research Report | en_EN |
| opus.affiliated | Lüssi, Felix | - |
| opus.affiliated | Zipp, Frauke | - |
| opus.affiliated | Jonuleit, Helmut | - |
| jgu.publisher.doi | 10.1371/journal.pone.0077634 | de |
| jgu.organisation.ror | https://ror.org/023b0x485 | - |
| Appears in collections: | DFG-OA-Publizieren (2012 - 2017) | |
Files in This Item:
| File | Description | Size | Format | ||
|---|---|---|---|---|---|
 | kinetics_of_il6_production_de-20220924212016766.pdf | 2.12 MB | Adobe PDF | View/Open |