The impact of fingolimod on Treg function in brain ischaemia

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dc.contributor.authorMalone, Kyleen
dc.contributor.authorShearer, Jennifer A.en
dc.contributor.authorWaeber, Christianen
dc.contributor.authorMoore, Anne C.en
dc.contributor.funderIrish Research Councilen
dc.contributor.funderHealth Research Boarden
dc.contributor.funderEuropean Regional Development Funden
dc.date.accessioned2024-02-29T09:29:46Z
dc.date.available2024-02-29T09:29:46Z
dc.date.issued2023en
dc.description.abstractFingolimod has generally shown neuroprotective effects in stroke models. Here, we tested the hypothesis that fingolimod modulates T-cell cytokine production towards a regulatory phenotype. Second, we investigated how fingolimod altered the Treg suppressive function and the sensitivity of effector T cells to regulation. Mice that had underwent the permanent electrocoagulation of the left middle cerebral artery received saline or fingolimod (0.5 mg/kg) daily for 10-days post-ischaemia. Fingolimod improved neurobehavioural recovery compared to saline control and increased Treg frequency in the periphery and brain. Tregs from fingolimod-treated animals had a higher expression of CCR8. Fingolimod increased the frequencies of CD4+ IL-10+ , CD4+ IFN-γ+ and CD4+ IL-10+ IFN-γ+ cells in spleen and blood, and CD4+ IL-17+ cells in the spleen, with only minor effects on CD8+ T-cell cytokine production. Treg from post-ischaemic mice had reduced suppressive function compared to Treg from non-ischaemic mice. Fingolimod treatment rescued this function against saline-treated but not fingolimod-treated CD4+ effector T cells. In conclusion, fingolimod seems to improve the suppressive function of Treg post-stroke while also increasing the resistance of CD4+ effector cells to this suppression. Fingolimod's capacity to increase both effector and regulatory functions may explain the lack of consistent improvement in functional recovery in experimental brain ischaemia.en
dc.description.sponsorshipIrish Research Council (Grant number GOIPG/2017/431); Health Research Board (Award HRA-POR-2015-1236); European Regional Development Fund (EAPA_791/2018, 2019–21)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleid2350370en
dc.identifier.citationMalone, K., Shearer, J.A., Waeber, C. and Moore, A.C. (2023) ‘The impact of fingolimod on Treg function in brain ischaemia’, European Journal of Immunology, 53(9), 2350370 (13pp) . doi: 10.1002/eji.202350370en
dc.identifier.doi10.1002/eji.202350370en
dc.identifier.endpage13en
dc.identifier.issued9en
dc.identifier.journaltitleEuropean Journal of Immunologyen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/15605
dc.identifier.volume53en
dc.language.isoenen
dc.publisherJohn Wiley and Sons Incen
dc.rights© 2023 The Authors. European Journal of Immunology published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License,which permits use, distribution and reproduction in any medium, provided the original work is properly citedand is not used for commercial purposes.en
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/en
dc.subjectFTY720en
dc.subjectFingolimoden
dc.subjectIschaemiaen
dc.subjectRegulatory T cellsen
dc.subjectStrokeen
dc.subjectTregen
dc.titleThe impact of fingolimod on Treg function in brain ischaemiaen
dc.typeArticle (peer-reviewed)en
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