{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T02:36:03Z","timestamp":1789698963656,"version":"4.0.1"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T00:00:00Z","timestamp":1621814400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005946","name":"Hokkaido University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005946","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"AMED","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007802","name":"Institute for Fermentation, Osaka","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007802","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004398","name":"Mitsubishi Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004398","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008732","name":"Uehara Memorial Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008732","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Tokyo Biomedical Research Foundation"},{"DOI":"10.13039\/100000072","name":"NIDCR","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["1ZIADE000695"],"award-info":[{"award-number":["1ZIADE000695"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,7,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Sj\u00f6gren\u2019s syndrome (SS) is an autoimmune disease characterized by inflammation with lymphoid infiltration and destruction of the salivary glands. Although many genome-wide association studies have revealed disease-associated risk alleles, the functions of the majority of these alleles are unclear. Here, we show previously unrecognized roles of GTF2I molecules by using two SS-associated single nucleotide polymorphisms (SNPs), rs73366469 and rs117026326 (GTF2I SNPs). We found that the risk alleles of GTF2I SNPs increased GTF2I expression and enhanced nuclear factor-kappa B (NF-\u03baB) activation in human salivary gland cells via the NF-\u03baB p65 subunit. Indeed, the knockdown of GTF2I suppressed inflammatory responses in mouse endothelial cells and in vivo. Conversely, the over-expression of GTF2I enhanced NF-\u03baB reporter activity depending on its p65-binding N-terminal leucine zipper domain. GTF2I is highly expressed in the human salivary gland cells of SS patients expressing the risk alleles. Consistently, the risk alleles of GTF2I SNPs were strongly associated with activation of the IL-6 amplifier, which is hyperactivation machinery of the NF-\u03baB pathway, and lymphoid infiltration in the salivary glands of SS patients. These results demonstrated that GTF2I expression in salivary glands is increased in the presence of the risk alleles of GTF2I SNPs, resulting in activation of the NF-\u03baB pathway in salivary gland cells. They also suggest that GTF2I could be a new therapeutic target for SS.<\/jats:p>","DOI":"10.1093\/intimm\/dxab025","type":"journal-article","created":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T11:10:55Z","timestamp":1621595455000},"page":"423-434","source":"Crossref","is-referenced-by-count":17,"title":["Sj\u00f6gren\u2019s syndrome-associated SNPs increase GTF2I expression in salivary gland cells to enhance inflammation development"],"prefix":"10.1093","volume":"33","author":[{"given":"Shuhei","family":"Shimoyama","sequence":"first","affiliation":[{"name":"Division of Molecular Psychoimmunology, Institute for Genetic Medicine, Hokkaido University , Sapporo 0600815 , Japan"},{"name":"Department of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine , Sapporo 0600815 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikuma","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Division of Molecular Psychoimmunology, Institute for Genetic Medicine, Hokkaido University , Sapporo 0600815 , Japan"},{"name":"Department of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine , Sapporo 0600815 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Jing","family":"Jiang","sequence":"additional","affiliation":[{"name":"Division of Molecular Psychoimmunology, Institute for Genetic Medicine, Hokkaido University , Sapporo 0600815 , Japan"},{"name":"Institute of Preventive Genomic Medicine, School of Life Sciences, Northwest University , Xian 710069 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isao","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Division of Clinical Immunology, Major of Advanced Biological Applications, Graduate School Comprehensive Human Science, University of Tsukuba , Tsukuba 3050006 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A","family":"Chiorini","sequence":"additional","affiliation":[{"name":"AAV Biology Section, Division of Intramural Research, National Institute of Dental and Craniofacial Research, National Institutes of Health , Bethesda, MD 20892 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinori","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Omics Research, Department of Applied Genomics, Kazusa DNA Research Institute , 2-6-7 Kazusa-kamatari, Kisarazu, Chiba 2920818 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Ohara","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Omics Research, Department of Applied Genomics, Kazusa DNA Research Institute , 2-6-7 Kazusa-kamatari, Kisarazu, Chiba 2920818 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rie","family":"Hasebe","sequence":"additional","affiliation":[{"name":"Biomedical Animal Research Laboratory, Institute for Genetic Medicine, Hokkaido University , Sapporo 0600815 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsutoshi","family":"Ota","sequence":"additional","affiliation":[{"name":"Division of Molecular Psychoimmunology, Institute for Genetic Medicine, Hokkaido University , Sapporo 0600815 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona","family":"Uchida","sequence":"additional","affiliation":[{"name":"Division of Molecular Psychoimmunology, Institute for Genetic Medicine, Hokkaido University , Sapporo 0600815 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Kamimura","sequence":"additional","affiliation":[{"name":"Division of Molecular Psychoimmunology, Institute for Genetic Medicine, Hokkaido University , Sapporo 0600815 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shintaro","family":"Hojyo","sequence":"additional","affiliation":[{"name":"Division of Molecular Psychoimmunology, Institute for Genetic Medicine, Hokkaido University , Sapporo 0600815 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Division of Molecular Psychoimmunology, Institute for Genetic Medicine, Hokkaido University , Sapporo 0600815 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Atsumi","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine , Sapporo 0600815 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaaki","family":"Murakami","sequence":"additional","affiliation":[{"name":"Division of Molecular Psychoimmunology, Institute for Genetic 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