{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T22:40:22Z","timestamp":1790980822045,"version":"4.1.0"},"reference-count":58,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,1,18]],"date-time":"2013-01-18T00:00:00Z","timestamp":1358467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2013,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Plasticity of <jats:styled-content style=\"fixed-case\">CD4<jats:sup>+<\/jats:sup><\/jats:styled-content> lymphocyte Th17\/regulatory T cell (Treg) subsets is involved in the pathogenesis of chronic airway inflammatory diseases, such as asthma. Reversal of Th17\/Treg cell balance towards Treg cells may be beneficial for the suppression of chronic Th2 cell\u2010mediated inflammatory diseases, such as asthma. However, the effect of the combination of corticosteroids and a statin on the ratio of Treg\/Th17 cells is unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>We investigated the <jats:italic>in vitro<\/jats:italic> effects of the combination of simvastatin and fluticasone propionate (<jats:styled-content style=\"fixed-case\">FP<\/jats:styled-content>) on the numbers of Treg and Th17 cells in asthmatic patients after co\u2010incubation with monocyte\u2010derived DCs (<jats:styled-content style=\"fixed-case\">mDC<\/jats:styled-content>s), and explored the underlying signalling pathways involved.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using flow cytometry, we determined the effects of <jats:styled-content style=\"fixed-case\">FP<\/jats:styled-content> and simvastatin on Treg\/Th17 balance after co\u2010incubation of asthmatic <jats:styled-content style=\"fixed-case\">CD4<jats:sup>+<\/jats:sup><\/jats:styled-content> T cells with <jats:styled-content style=\"fixed-case\">mDC<\/jats:styled-content>s. We also measured the relevant Treg and Th17\u2010polarizing cytokines released from <jats:styled-content style=\"fixed-case\">mDC<\/jats:styled-content>s and also investigated the role of indoleamine 2, 3\u2010dioxygenase (<jats:styled-content style=\"fixed-case\">IDO<\/jats:styled-content>) in this response.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The combination of simvastatin and <jats:styled-content style=\"fixed-case\">FP<\/jats:styled-content> significantly increased Treg and concomitantly reduced Th17 cell numbers to a greater extent than <jats:styled-content style=\"fixed-case\">FP<\/jats:styled-content> or statin treatment alone. The enhancing effects of simvastatin on <jats:styled-content style=\"fixed-case\">FP<\/jats:styled-content> effects were mediated through the up\u2010regulation of indoleamine 2, 3\u2010dioxygenase and interleukin (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>)\u201010, together with down\u2010regulation of IL\u20106 and IL\u201023 expression in <jats:styled-content style=\"fixed-case\">mDC<\/jats:styled-content>s.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>On the basis of this <jats:italic>in vitro<\/jats:italic> model of asthma, we suggest that the combination of a statin and a corticosteroid could augment the Treg\/Th17 cell ratio and thus more effectively suppress airway inflammation in asthma patients. This may be particularly relevant in the treatment of severe asthma where Th17 cells are activated and linked to neutrophilic inflammation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cea.12067","type":"journal-article","created":{"date-parts":[[2012,12,18]],"date-time":"2012-12-18T18:07:37Z","timestamp":1355854057000},"page":"212-222","source":"Crossref","is-referenced-by-count":58,"title":["Statins enhance the effects of corticosteroids on the balance between regulatory T cells and Th17 cells"],"prefix":"10.1111","volume":"43","author":[{"given":"K.","family":"Maneechotesuwan","sequence":"first","affiliation":[{"name":"Division of Respiratory Disease and Tuberculosis Department of Internal Medicine Faculty of Medicine Siriraj Hospital Mahidol University Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Kasetsinsombat","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Faculty of Medicine Siriraj Hospital Mahidol University Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Wamanuttajinda","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Faculty of Medicine Siriraj Hospital Mahidol University Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Wongkajornsilp","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Faculty of Medicine Siriraj Hospital Mahidol University Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. 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