{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T21:46:36Z","timestamp":1790027196931,"version":"4.0.1"},"reference-count":36,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2018,9,25]],"date-time":"2018-09-25T00:00:00Z","timestamp":1537833600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Drug\u2010induced hypersensitivity syndrome\/drug reaction with eosinophilia and systemic symptoms (Di<jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">DRESS<\/jats:styled-content>) is a distinct phenotype of severe drug eruptions characterized by sequential reactivations of herpesviruses. Although a progressive loss of suppressive function in regulatory T cells (Tregs) occurred during the course of <jats:styled-content style=\"fixed-case\">DiHS<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">DRESS<\/jats:styled-content>, but not in Stevens\u2010Johnson syndrome\/toxic epidermal necrolysis (<jats:styled-content style=\"fixed-case\">SJS<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">TEN<\/jats:styled-content>), no previous studies investigated the mechanism. Given the recent finding that Treg development could be differentially regulated by <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>16<jats:sup>+<\/jats:sup> patrolling monocytes (<jats:styled-content style=\"fixed-case\">pMO<\/jats:styled-content>s) and <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>14<jats:sup>+<\/jats:sup> classical monocytes (<jats:styled-content style=\"fixed-case\">cMO<\/jats:styled-content>s), we can hypothesize that a differential fine\u2010tuned interaction between Tregs and monocytes is the driving force behind the possible shift from Tregs to Th17 cells over a prolonged period of time in Di<jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content>\/DRESS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate whether the shift from Treg to Th17 could specifically occur during the course of Di<jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">DRESS<\/jats:styled-content> and to elucidate which subsets of monocytes could be involved in the shift.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a prospective longitudinal study on the frequencies of Tregs, Th17 cells and monocyte subsets after onset of Di<jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">DRESS<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">SJS<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">TEN<\/jats:styled-content>, and long after their clinical resolutions. We next examined whether <jats:styled-content style=\"fixed-case\">pMO<\/jats:styled-content>s and <jats:styled-content style=\"fixed-case\">cMO<\/jats:styled-content>s could have a strong impact on the Th17\/Treg differentiation and which cytokines could be crucial for the interaction between Th17\/Tregs and <jats:styled-content style=\"fixed-case\">MO<\/jats:styled-content> subsets, by in\u00a0vitro cocultures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Selective depletion of <jats:styled-content style=\"fixed-case\">pMO<\/jats:styled-content>s occurring at the acute stage of Di<jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">DRESS<\/jats:styled-content> was associated with the relative increase in the frequencies of <jats:styled-content style=\"fixed-case\">cMO<\/jats:styled-content>s producing <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201010 and it did drive Treg expansions. After clinical resolution, <jats:styled-content style=\"fixed-case\">pMO<\/jats:styled-content>s producing <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106 were alternatively recruited and contributed to the eventual shift from a Treg to Th17 responses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Clinical Relevance<\/jats:title><jats:p>The gradual shift from Treg to Th17 cell development observed during the clinical course of Di<jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">DRESS<\/jats:styled-content> is mediated by the predominance of <jats:styled-content style=\"fixed-case\">cMO<\/jats:styled-content>s at the acute stage and alternatively recruited <jats:styled-content style=\"fixed-case\">pMO<\/jats:styled-content>s at the resolution stage, respectively.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cea.13252","type":"journal-article","created":{"date-parts":[[2018,8,16]],"date-time":"2018-08-16T05:55:10Z","timestamp":1534398910000},"page":"1453-1463","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Monocytes are involved in the balance between regulatory T cells and Th17 cells in severe drug eruptions"],"prefix":"10.1111","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1221-3129","authenticated-orcid":false,"given":"Yukiko","family":"Ushigome","sequence":"first","affiliation":[{"name":"Department of Dermatology Kyorin University School of Medicine Mitaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiko","family":"Mizukawa","sequence":"additional","affiliation":[{"name":"Department of Dermatology Kyorin University School of Medicine Mitaka 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