{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:56:42Z","timestamp":1790661402578,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,6,19]],"date-time":"2019-06-19T00:00:00Z","timestamp":1560902400000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004160","name":"Mazandaran University of Medical Sciences","doi-asserted-by":"publisher","award":["MCBRCMAZUMS\u20103075"],"award-info":[{"award-number":["MCBRCMAZUMS\u20103075"]}],"id":[{"id":"10.13039\/501100004160","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The contribution of immune checkpoint receptors in the immunopathogenesis of various autoimmune diseases has been addressed in previous reports. In this study,\u00a0 the expression profile of T\u2010cell immunoglobulin and mucin\u2010domain containing\u20103 (Tim\u20103) and programmed cell death\u20101 (PD\u20101) checkpoint molecules was investigated\u00a0in CD8<jats:sup>+<\/jats:sup> T cells of Vitiligo patients. The association of Tim\u20103 and PD\u20101 expression with disease activity was also explored. The frequency of Tim\u20103<jats:sup>+<\/jats:sup>\/PD\u20101<jats:sup>+<\/jats:sup>\/CD8<jats:sup>+<\/jats:sup> T cells in 30 patients with vitiligo and 30 sex\u2010 and age\u2010matched controls was determined by flow cytometry. CD8<jats:sup>+<\/jats:sup> T cells were then positively isolated by magnetic beads, and the mRNA expression of PD\u20101 and Tim\u20103 was determined by TaqMan\u2010based real\u2010time PCR. To measure the cytokines production, PBMCs were stimulated with PMA\/ionomycin and concentrations of IL\u20104, IFN\u2010\u03b3 and TNF\u2010\u03b1 were measured in culture supernatants by ELISA. Disease activity of patients with vitiligo was determined using the Vitiligo Area Severity Index. Patients with vitiligo have significantly shown more expression of Tim\u20103 and PD\u20101 on their CD8<jats:sup>+<\/jats:sup> T cells compared with controls. Expression analysis of Tim\u20103 mRNA, but not PD\u20101, confirmed the results obtained from flow cytometry. While the production levels of TNF\u2010\u03b1 and IFN\u2010\u03b3 were found higher by patients with vitiligo, IL\u20104 production was lower in patients compared with controls. A direct association was observed between the Tim\u20103 and PD\u20101 expression and also the production of pro\u2010inflammatory cytokines with disease activity of patients with vitiligo. Our results indicate that Tim\u20103 and PD\u20101 are involved in immune dysregulation mechanisms of CD8<jats:sup>+<\/jats:sup> T cells in vitiligo and may introduce as potential biomarkers for disease progression and targeted immunotherapy.<\/jats:p>","DOI":"10.1111\/exd.13952","type":"journal-article","created":{"date-parts":[[2019,5,2]],"date-time":"2019-05-02T12:55:02Z","timestamp":1556801702000},"page":"674-681","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Expression analysis of PD\u20101 and Tim\u20103 immune checkpoint receptors in patients with vitiligo; positive association with disease activity"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3742-358X","authenticated-orcid":false,"given":"Ali","family":"Rahimi","sequence":"first","affiliation":[{"name":"Department of Immunology School of Medicine Mazandaran University of Medical Sciences Sari Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadi","family":"Hossein\u2010Nataj","sequence":"additional","affiliation":[{"name":"Department of Immunology School of Medicine Mazandaran University of Medical Sciences Sari Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zohreh","family":"Hajheydari","sequence":"additional","affiliation":[{"name":"Department of Dermatology Faculty of Medicine Mazandaran University of Medical Sciences Sari Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeinab","family":"Aryanian","sequence":"additional","affiliation":[{"name":"Department of Dermatology Faculty of Medicine Babol University of Medical Sciences Babol Iran"},{"name":"Autoimmune Bullous Diseases Research Center Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asghar","family":"Shayannia","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology School of Medicine Shahroud University of Medical Sciences Shahroud Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abolghasem","family":"Ajami","sequence":"additional","affiliation":[{"name":"Department of Immunology School of Medicine Mazandaran University of Medical Sciences Sari Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3816-8792","authenticated-orcid":false,"given":"Hossein","family":"Asgarian\u2010Omran","sequence":"additional","affiliation":[{"name":"Department of Immunology School of Medicine Mazandaran University of Medical Sciences Sari Iran"},{"name":"Gastrointestinal Cancer Research Center Mazandaran University of Medical Sciences Sari Mazandaran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,6,19]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-017-8622-7"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.2174\/138920010791526105"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1346-8138.2010.01139.x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.det.2016.11.014"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/1346-8138.12147"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/jidsymp.2015.8"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOP.0000000000000375"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.2340\/00015555-2080"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/exd.13069"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2014.04.010"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00418"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2012.01136.x"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00403-016-1665-4"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.12880"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00472"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2016.12.002"},{"key":"e_1_2_8_18_1","first-page":"2269","volume":"18","author":"Taghiloo S.","year":"2017","journal-title":"Asian Pac. 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