{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:14:09Z","timestamp":1791591249443,"version":"4.3.4"},"reference-count":30,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2018,10,24]],"date-time":"2018-10-24T00:00:00Z","timestamp":1540339200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008903","name":"Ministry of Health and Welfare","doi-asserted-by":"publisher","award":["HI13C0016"],"award-info":[{"award-number":["HI13C0016"]}],"id":[{"id":"10.13039\/100008903","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis & Rheumatology"],"published-print":{"date-parts":[[2018,12]]},"abstract":"\n Objective<\/jats:title>\n \n To examine whether a\n JAK<\/jats:styled-content>\n inhibitor regulates functional responses of human salivary gland epithelial cells (\n SGEC<\/jats:styled-content>\n s) and disease parameters in an animal model of Sj\u00f6gren's syndrome (\n SS<\/jats:styled-content>\n ).\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Common differentially expressed genes (\n DEG<\/jats:styled-content>\n s) were analyzed among peripheral blood mononuclear cells from patients with primary\n SS<\/jats:styled-content>\n and other data sets, using blood and\n SG<\/jats:styled-content>\n tissue. Validation of expression in\n SG<\/jats:styled-content>\n s was analyzed by focus score. Inhibition of messenger\n RNA<\/jats:styled-content>\n expression of\n DEG<\/jats:styled-content>\n s and\n \n BAFF<\/jats:styled-content>\n <\/jats:italic>\n by filgotinib was analyzed using reverse transcription\u2013polymerase chain reaction in primary\n SGEC<\/jats:styled-content>\n s.\n SG<\/jats:styled-content>\n organoid cultures were used to determine the association between\n DEG<\/jats:styled-content>\n s and\n BAFF<\/jats:styled-content>\n via knockdown using small interfering\n RNA<\/jats:styled-content>\n s or to determine regulation of\n BAFF<\/jats:styled-content>\n by\n JAK<\/jats:styled-content>\n inhibitor. Filgotinib (1.5 mg\/kg) was intraperitoneally injected into 8\u2010week\u2010old\n NOD<\/jats:styled-content>\n \/ShiLtJ mice 3 times per week to analyze manifestations of disease. Finally,\n STAT<\/jats:styled-content>\n signaling was assessed in human and mouse\n SGEC<\/jats:styled-content>\n s.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Expression of the\n DEG<\/jats:styled-content>\n s\n \n IFNG<\/jats:styled-content>\n <\/jats:italic>\n and\n \n BAFF<\/jats:styled-content>\n <\/jats:italic>\n increased in\n SG<\/jats:styled-content>\n s from patients with primary\n SS<\/jats:styled-content>\n , as assessed by focus score. There was a significant correlation between\n \n IFIT<\/jats:styled-content>\n 2\n <\/jats:italic>\n and\n \n BAFF<\/jats:styled-content>\n <\/jats:italic>\n expression.\n JAK<\/jats:styled-content>\n inhibitor suppressed interferon (\n IFN<\/jats:styled-content>\n )\u2013induced transcription of\n DEG<\/jats:styled-content>\n s and\n \n BAFF<\/jats:styled-content>\n <\/jats:italic>\n in human primary\n SGEC<\/jats:styled-content>\n s. Knockdown of\n DEG<\/jats:styled-content>\n s or inhibition of\n JAK<\/jats:styled-content>\n caused reduced secretion of\n BAFF<\/jats:styled-content>\n in\u00a0human\n SG<\/jats:styled-content>\n organoid cultures. In addition, filgotinib\u2010treated mice exhibited increased salivary flow rates and marked reductions in lymphocytic infiltration of\n SG<\/jats:styled-content>\n s.\n JAK<\/jats:styled-content>\n inhibitor regulated\n IFN<\/jats:styled-content>\n \u03b1\u2010 and\n IFN<\/jats:styled-content>\n \u03b3\u2010induced\n pSTAT<\/jats:styled-content>\n \u20101\n Y701<\/jats:sub>\n ,\n pSTAT<\/jats:styled-content>\n \u20103\n Y705<\/jats:sub>\n , and protein inhibitor of activated\n STAT<\/jats:styled-content>\n \u20103 (\n PIAS<\/jats:styled-content>\n \u20103) in human\n SGEC<\/jats:styled-content>\n s as well as\n IFN<\/jats:styled-content>\n \u03b3\u2010induced\n pSTAT<\/jats:styled-content>\n \u20101\n Y701<\/jats:sub>\n ,\n pSTAT<\/jats:styled-content>\n \u20103\n S727<\/jats:sub>\n , and\n PIAS<\/jats:styled-content>\n \u20101 in mouse SGECs.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n JAK<\/jats:styled-content>\n inhibition controls aberrant activation of\n SGEC<\/jats:styled-content>\n s and may be a novel therapeutic approach for primary\n SS<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/art.40589","type":"journal-article","created":{"date-parts":[[2018,6,21]],"date-time":"2018-06-21T07:59:46Z","timestamp":1529567986000},"page":"2057-2066","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":81,"title":["JAK<\/scp>\n \u20101 Inhibition Suppresses Interferon\u2010Induced\n BAFF<\/scp>\n Production in Human Salivary Gland"],"prefix":"10.1002","volume":"70","author":[{"given":"Jaeseon","family":"Lee","sequence":"first","affiliation":[{"name":"The Catholic University of Korea Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Lee","sequence":"additional","affiliation":[{"name":"The Catholic University of Korea Seoul St. Mary's Hospital Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung\u2010Ki","family":"Kwok","sequence":"additional","affiliation":[{"name":"The Catholic University of Korea Seoul St. Mary's Hospital Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SeungYe","family":"Baek","sequence":"additional","affiliation":[{"name":"The Catholic University of Korea Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Se Gwang","family":"Jang","sequence":"additional","affiliation":[{"name":"The Catholic University of Korea Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung\u2010Min","family":"Hong","sequence":"additional","affiliation":[{"name":"The Catholic University of Korea Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae\u2010Woong","family":"Min","sequence":"additional","affiliation":[{"name":"Kangwon National University Chuncheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun Shim","family":"Choi","sequence":"additional","affiliation":[{"name":"Kangwon National University Chuncheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juhyun","family":"Lee","sequence":"additional","affiliation":[{"name":"The Catholic University of Korea Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi\u2010La","family":"Cho","sequence":"additional","affiliation":[{"name":"The Catholic University of Korea Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung\u2010Hwan","family":"Park","sequence":"additional","affiliation":[{"name":"The Catholic University of Korea Seoul St. Mary's Hospital Seoul Republic of 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