{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T17:28:47Z","timestamp":1777829327094,"version":"3.51.4"},"reference-count":42,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,2,13]],"date-time":"2014-02-13T00:00:00Z","timestamp":1392249600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust, UK","doi-asserted-by":"crossref","award":["086827"],"award-info":[{"award-number":["086827"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust, UK","doi-asserted-by":"crossref","award":["080088"],"award-info":[{"award-number":["080088"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NIH","award":["DE022550"],"award-info":[{"award-number":["DE022550"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2014,4]]},"abstract":"<jats:p><jats:italic>Candida albicans<\/jats:italic> remains the fungus most frequently associated with nosocomial bloodstream infection. In disseminated candidiasis, the role of Foxp3<jats:sup>+<\/jats:sup> regulatory T (Treg) cells remains largely unexplored. Our aims were to characterize Foxp3<jats:sup>+<\/jats:sup> Treg\u2010cell activation in a murine intravenous challenge model of disseminated <jats:italic>C. albicans<\/jats:italic> infection, and determine the contribution to disease. Flow cytometric analyses demonstrated that <jats:italic>C. albicans<\/jats:italic> infection drove in vivo expansion of a splenic CD4<jats:sup>+<\/jats:sup>Foxp3<jats:sup>+<\/jats:sup> population that correlated positively with fungal burden. Depletion from Foxp3<jats:sup>hCD2<\/jats:sup> reporter mice in vivo confirmed that Foxp3<jats:sup>+<\/jats:sup> cells exacerbated fungal burden and inflammatory renal disease. The CD4<jats:sup>+<\/jats:sup>Foxp3<jats:sup>+<\/jats:sup> population expanded further after in vitro stimulation with <jats:italic>C. albicans<\/jats:italic> antigens (Ags), and included at least three cell types. These arose from proliferation of the natural Treg\u2010cell subset, together with conversion of Foxp3<jats:sup>\u2212<\/jats:sup> cells to the induced Treg\u2010cell form, and to a cell type sharing effector Th17\u2010cell characteristics, expressing ROR\u2010\u03b3t, and secreting IL\u201017A. The expanded Foxp3<jats:sup>+<\/jats:sup> T cells inhibited Th1 and Th2 responses, but enhanced Th17\u2010cell responses to <jats:italic>C. albicans<\/jats:italic> Ags in vitro, and in vivo depletion confirmed their ability to enhance the Th17\u2010cell response. These data lead to a model for disseminated candidiasis whereby expansion of Foxp3<jats:sup>+<\/jats:sup> T cells promotes Th17\u2010cell responses that drive pathology.<\/jats:p>","DOI":"10.1002\/eji.201343604","type":"journal-article","created":{"date-parts":[[2014,1,17]],"date-time":"2014-01-17T00:46:52Z","timestamp":1389919612000},"page":"1069-1083","source":"Crossref","is-referenced-by-count":58,"title":["Expansion of Foxp3<sup>+<\/sup> T\u2010cell populations by <i>Candida albicans<\/i> enhances both Th17\u2010cell responses and fungal dissemination after intravenous challenge"],"prefix":"10.1002","volume":"44","author":[{"given":"Natasha","family":"Whibley","sequence":"first","affiliation":[{"name":"Division of Applied Medicine University of Aberdeen  Aberdeen UK"},{"name":"Aberdeen Fungal Group University of Aberdeen  Aberdeen UK"},{"name":"Division of Rheumatology and Clinical Immunology University of Pittsburgh  Pittsburgh PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donna M.","family":"MacCallum","sequence":"additional","affiliation":[{"name":"Aberdeen Fungal Group University of Aberdeen  Aberdeen UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark A.","family":"Vickers","sequence":"additional","affiliation":[{"name":"Academic Transfusion Medicine Unit Scottish National Blood Transfusion Service  Aberdeen UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sadia","family":"Zafreen","sequence":"additional","affiliation":[{"name":"Department of Pathology NHS Grampian  Aberdeen UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Herman","family":"Waldmann","sequence":"additional","affiliation":[{"name":"Sir William Dunn School of Pathology University of Oxford  Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shohei","family":"Hori","sequence":"additional","affiliation":[{"name":"Research Unit for Immune Homeostasis RIKEN Research Center for Allergy and Immunology  Yokohama City Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah L.","family":"Gaffen","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology University of Pittsburgh  Pittsburgh PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neil A. 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