{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:38:20Z","timestamp":1773794300385,"version":"3.50.1"},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T00:00:00Z","timestamp":1739836800000},"content-version":"vor","delay-in-days":48,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81571594"],"award-info":[{"award-number":["81571594"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071842"],"award-info":[{"award-number":["82071842"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFC2702001"],"award-info":[{"award-number":["2021YFC2702001"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Immunology Research"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>\n                    <jats:bold>Objectives:<\/jats:bold>\n                    Primary Sj\u00f6gren\u2019s syndrome (pSS) is associated with a risk allele T of rs117026326 located at a potential splicing enhancer within the intronic region of general transcription factor II\u2010I (GTF2I). This study aimed to explore the rs117026326\u2010regulated alternative splicing of GTF2I and its role in B cell overactivation in pSS.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    GTF2I isoform expressions and rs117026326 genotypes of pSS peripheral blood mononuclear cells (PBMCs) were examined using quantitative PCR and Sanger sequencing, respectively. GTF2I\u0394 was overexpressed in B cells, T cells, and macrophages using plasmid transfection. Proliferation of B cells and T cells was determined using Cell Counting Kit\u20108 (CCK8) assay. CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell differentiation was inspected using flow cytometry. Proinflammatory cytokine production of macrophages was investigated using quantitative PCR. c\u2010FOS expression in GTF2I\u0394\u2010transfected B cells was tested by quantitative PCR, and proliferation of GTF2I\u0394\u2010transfected B cells treated with c\u2010FOS siRNA or c\u2010FOS inhibitor was interrogated using CCK8 assay.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    pSS patients with risk allele of rs117026326 expressed higher levels of GTF2I\u0394 and GTF2I\u03b6 isoforms. GTF2I\u0394 expression was correlated with serum immunoglobulin G (IgG). GTF2I\u0394 promoted B cell proliferation and upregulated c\u2010FOS expression. Knocking down or inhibition of c\u2010FOS reversed B cell proliferation driven by GTF2I\u0394.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    pSS risk allele of rs117026326 modulates alternative splicing of GTF2I and upregulates GTF2I\u0394 isoform, which promotes B cell proliferation through enhancing binding and transcription of c\u2010FOS.\n                  <\/jats:p>","DOI":"10.1155\/jimr\/4821639","type":"journal-article","created":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T03:19:39Z","timestamp":1739848779000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Risk Allele rs117026326\u2010Mediated Alternative Splicing of GTF2I Promotes B Cell Proliferation in Primary Sj\u00f6gren\u2019s 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