{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T12:58:15Z","timestamp":1788785895198,"version":"build-2803163510"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T00:00:00Z","timestamp":1753228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genome Ed."],"abstract":"<jats:p>Sj\u00f6gren\u2019s disease (SD) is a systemic autoimmune disease that particularly affects the salivary and lacrimal glands, causing sicca symptoms. Genetic polymorphism in the <jats:italic>TNFAIP3<\/jats:italic> gene has been implicated in the pathogenesis of SD. In this study, we aimed to functionally determine the impact of two specific single-nucleotide polymorphisms (SNPs) in <jats:italic>TNFAIP3<\/jats:italic>, rs6920220 (G\/A) and rs2230926 (T\/C\/G), on the pathogenesis of SD. Using CRISPR-Cas9, we edited human salivary gland epithelial cells (SGECs) to incorporate <jats:italic>TNFAIP3<\/jats:italic> SNPs rs6920220 (G\/A) and rs2230926 (T\/C\/G) and co-cultured them with Jurkat cells. We performed assays to examine gene expression, inflammatory cytokine levels, and related signaling pathways to investigate the effects of these genetic variants on <jats:italic>TNFAIP3<\/jats:italic> function and cellular response. Our results demonstrated that these SNPs reduced <jats:italic>TNFAIP3<\/jats:italic> expression, increased NF-\u03baB activation, and elevated pro-inflammatory cytokine production. These findings provide strong evidence for the functional significance of these genetic variants in the pathogenesis of SD and underscore the utility of CRISPR-Cas9 technology in elucidating genetic contributions to autoimmune disorders.<\/jats:p>","DOI":"10.3389\/fgeed.2025.1625393","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T08:24:06Z","timestamp":1753259046000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["CRISPR-Cas9 editing of TNFAIP3 variants in salivary gland epithelial cells to study Sj\u00f6gren\u2019s disease pathogenesis"],"prefix":"10.3389","volume":"7","author":[{"given":"Subhashis","family":"Ghosh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qisheng","family":"Tu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoe Xiaofang","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sreelakshmi","family":"Panginikkod","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jake Jinkun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2561","DOI":"10.1093\/rheumatology\/key360","article-title":"Innate immunity and interferons in the pathogenesis of Sj\u00f6gren's syndrome","volume":"60","author":"Bodewes","year":"2021","journal-title":"Rheumatol. 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