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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\u00a0mg\/kg) daily for 10\u2010days post\u2010ischaemia. Fingolimod improved neurobehavioural recovery compared to saline control and increased Treg frequency in the periphery and brain. Tregs from fingolimod\u2010treated animals had a higher expression of CCR8. Fingolimod increased the frequencies of CD4\n                    <jats:sup>+<\/jats:sup>\n                    IL\u201010\n                    <jats:sup>+<\/jats:sup>\n                    , CD4\n                    <jats:sup>+<\/jats:sup>\n                    IFN\u2010\u03b3\n                    <jats:sup>+<\/jats:sup>\n                    and CD4\n                    <jats:sup>+<\/jats:sup>\n                    IL\u201010\n                    <jats:sup>+<\/jats:sup>\n                    IFN\u2010\u03b3\n                    <jats:sup>+<\/jats:sup>\n                    cells in spleen and blood, and CD4\n                    <jats:sup>+<\/jats:sup>\n                    IL\u201017\n                    <jats:sup>+<\/jats:sup>\n                    cells in the spleen, with only minor effects on CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell cytokine production. Treg from post\u2013ischaemic mice had reduced suppressive function compared to\u00a0Treg from non\u2010ischaemic mice. Fingolimod treatment rescued this function against saline\u2010treated but not fingolimod\u2010treated CD4\n                    <jats:sup>+<\/jats:sup>\n                    effector T cells. In conclusion, fingolimod seems to improve the suppressive function of Treg post\u2010stroke while also increasing the resistance of CD4\n                    <jats:sup>+<\/jats:sup>\n                    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.\n                  <\/jats:p>","DOI":"10.1002\/eji.202350370","type":"journal-article","created":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T06:55:41Z","timestamp":1687848941000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The impact of fingolimod on Treg function in brain ischaemia"],"prefix":"10.1002","volume":"53","author":[{"given":"Kyle","family":"Malone","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Therapeutics, Western Gateway Building University College Cork Cork Ireland"},{"name":"School of Pharmacy University College Cork Cork Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer A.","family":"Shearer","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, Western Gateway Building University College Cork Cork Ireland"},{"name":"School of Pharmacy University College Cork Cork Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Waeber","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, Western Gateway Building University College Cork Cork Ireland"},{"name":"School of Pharmacy University College Cork Cork Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3656-4230","authenticated-orcid":false,"given":"Anne C.","family":"Moore","sequence":"additional","affiliation":[{"name":"School of Biochemistry and Cell Biology University College Cork Cork Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,6,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.2010.481671"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02284"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.2179"},{"key":"e_1_2_9_5_1","first-page":"1","article-title":"Efficacy of the sphingosine\u20101\u2010phosphate receptor agonist fingolimod in animal models of stroke: an updated meta\u2010analysis","author":"Dang C.","year":"2020","journal-title":"Int. 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