{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:24:05Z","timestamp":1790745845548,"version":"4.1.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2015,8,1]],"date-time":"2015-08-01T00:00:00Z","timestamp":1438387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular damage and fibrosis of the skin and internal organs. Because activated and oligoclonally expanded CD8+ T cells can be detected in peripheral blood and lungs of SSc patients, effector memory CD8+ T cells may play a critical role for organ involvement in SSc; however, the pathogenic functions of effector memory CD8+ T cells remain incompletely understood. In this study, we performed DNA microarray analysis of the sort-purified effector memory CD8+ T cells from SSc patients and healthy controls, and showed that the expression of genes related to immune response and cell adhesion, including CD226 (also known as DNAX accessory molecule-1 [DNAM-1]), was significantly altered. Moreover, detailed analysis of CD226 revealed that CD226highCD8+ T cells were increased in SSc patients (mean, 50.7%) compared with healthy controls (32.9%) and were appreciably associated with the severity of skin sclerosis and interstitial lung disease. Furthermore, CD226+CD8+ T cells produced higher amount of various cytokines than CD226\u2212 ones, and CD226highCD8+ T cells from SSc patients showed upregulated IL-13 production and positive correlation with the cytotoxic capacity of CD8+ T cells against HUVECs. Finally, the neutralization of CD226 in CD8+ T cells impaired costimulation, cytokine productions, and cytolysis against HUVECs. These findings indicate that upregulated CD226 expression on CD8+ T cells reflects disease severity and is involved in SSc pathogenesis via the production of various cytokines, including profibrotic IL-13 and endothelial cell injury, and that CD226 may be a useful target in the treatment of SSc.<\/jats:p>","DOI":"10.4049\/jimmunol.1403046","type":"journal-article","created":{"date-parts":[[2015,6,25]],"date-time":"2015-06-25T01:36:11Z","timestamp":1435196171000},"page":"892-900","source":"Crossref","is-referenced-by-count":57,"title":["Increased CD226 Expression on CD8+ T Cells Is Associated with Upregulated Cytokine Production and Endothelial Cell Injury in Patients with Systemic Sclerosis"],"prefix":"10.1093","volume":"195","author":[{"given":"Masahiro","family":"Ayano","sequence":"first","affiliation":[{"name":"Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences , Fukuoka 812-8582 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Tsukamoto","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences , Fukuoka 812-8582 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Kohno","sequence":"additional","affiliation":[{"name":"Department of Hematology, National Kyushu Medical Center , Fukuoka 810-8563 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoyasu","family":"Ueda","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Miyazaki Prefectural Miyazaki Hospital , Miyazaki 880-8510 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences , Fukuoka 812-8582 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Mitoma","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences , Fukuoka 812-8582 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuteru","family":"Akahoshi","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences , Fukuoka 812-8582 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yojiro","family":"Arinobu","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences , Fukuoka 812-8582 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Niiro","sequence":"additional","affiliation":[{"name":"Clinical Education Center, Kyushu University Hospital , Fukuoka 812-8582 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiko","family":"Horiuchi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Kyushu University Beppu Hospital , Beppu 874-0836 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Akashi","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences , Fukuoka 812-8582 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,8,1]]},"reference":[{"key":"2025030703570705100_r1","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1056\/NEJMra0806188","article-title":"Scleroderma","volume":"360","author":"Gabrielli","year":"2009","journal-title":"N. 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