{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:11:22Z","timestamp":1792113082044,"version":"4.4.0"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,8,3]],"date-time":"2013-08-03T00:00:00Z","timestamp":1375488000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Ophthalmologica"],"published-print":{"date-parts":[[2014,2]]},"abstract":"<jats:title>Abstract.<\/jats:title><jats:p><jats:bold>Purpose:\u2002<\/jats:bold> This study aims to investigate the effects of systemic application of sphingosine 1\u2010phosphate receptor 1(S1P1) on allogeneic corneal transplantation in mice.<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold> A total of 112 BALB\/c mice received corneal grafts from C57BL\/6 donors. Recipients were randomly divided into seven groups and treated with intraperitoneal injections of S1P1 (5\u2003mg\/kg\/days), cyclosporine A (5\u2003mg\/kg\/days), dexamethasone (1\u2003mg\/kg\/days) and rapamycin (2\u2003mg\/kg\/days). S1P1was combined with rapamycin or cyclosporine A, and saline served as negative control. Serum levels of IL\u20102, IL\u201010, TGF\u2010<jats:italic>\u03b2<\/jats:italic>1 and IFN\u2010\u03b3 were measured by Elisa. The numbers of CD4+ T and regulatory (Treg) cell phenotype were measured by flow cytometry. Cytokine mRNA expression was analysed by real\u2010time quantitative PCR. CD4+ T cells and cytokines were histologically identified by immunofluorescence staining.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> Corneal graft survival was prolonged by intraperitoneal injections in S1P1 alone (mean survival time MST, 35.3\u2003\u00b1\u20035.6\u2003days), S1P1 combined with rapamycin (MST, 38.7\u2003\u00b1\u20036.5\u2003days) or S1P1 and cyclosporine A (MST, 32.7\u2003\u00b1\u20034.8\u2003days) compared with the controls (MST, 14.6\u2003\u00b1\u20030.2\u2003days; <jats:italic>n<\/jats:italic>\u2003=\u20035, p\u2003&lt;\u20030.01). S1P1 alone increased CD4+ T (p\u2003&lt;\u20030.01) and Treg cells (p\u2003&lt;\u20030.01; <jats:italic>n<\/jats:italic>\u2003=\u20035) in the cervical and mesenteric lymph nodes compared with the controls and S1P1\u2003+\u2003rapamycin (p\u2003&lt;\u20030.05; n\u2003=\u20035). TGF\u2010<jats:italic>\u03b2<\/jats:italic>1 and IL\u201010 mRNA transcriptions in corneal grafts following S1P1+ rapamycin increased (both p\u2003&lt;\u20030.01; <jats:italic>n<\/jats:italic>\u2003=\u20033), and TGF\u2010<jats:italic>\u03b2<\/jats:italic>1 and IL\u201010 in the serum level following S1P1 alone increased (both p\u2003&lt;\u20030.01; <jats:italic>n<\/jats:italic>\u2003=\u20033). These results paralleled the findings obtained from immunofluorescence.<\/jats:p><jats:p><jats:bold>Conclusion:\u2002<\/jats:bold> S1P1 has significant effect in corneal allograft rejection inhibition. The combined treatment of S1P1 and rapamycin results in synergistic effect.<\/jats:p>","DOI":"10.1111\/aos.12237","type":"journal-article","created":{"date-parts":[[2013,8,3]],"date-time":"2013-08-03T06:05:09Z","timestamp":1375509909000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Systemic application of sphingosine 1\u2010phosphate receptor 1 immunomodulator inhibits corneal allograft rejection in 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