Ghosh Subhashis, Tu Qisheng, Zhu Zoe Xiaofang, Panginikkod Sreelakshmi, Chen Jake Jinkun
Basic and Clinical Translational Sciences, Tufts Graduate School of Biomedical Sciences, Tufts University School of Medicine, Boston, MA, United States.
Tufts Medical Center Rheumatology, Boston, MA, United States.
Front Genome Ed. 2025 Jul 23;7:1625393. doi: 10.3389/fgeed.2025.1625393. eCollection 2025.
Sjögren's disease (SD) is a systemic autoimmune disease that particularly affects the salivary and lacrimal glands, causing sicca symptoms. Genetic polymorphism in the 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 , 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 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 function and cellular response. Our results demonstrated that these SNPs reduced expression, increased NF-κB 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.
干燥综合征（SD）是一种全身性自身免疫性疾病，特别影响唾液腺和泪腺，导致干燥症状。该基因的遗传多态性与干燥综合征的发病机制有关。在本研究中，我们旨在从功能上确定该基因中两个特定的单核苷酸多态性（SNP），即rs6920220（G/A）和rs2230926（T/C/G）对干燥综合征发病机制的影响。我们使用CRISPR-Cas9编辑人类唾液腺上皮细胞（SGEC），使其包含SNP rs6920220（G/A）和rs2230926（T/C/G），并将它们与Jurkat细胞共培养。我们进行了检测以检查基因表达、炎性细胞因子水平和相关信号通路，以研究这些基因变异对功能和细胞反应的影响。我们的结果表明，这些SNP降低了表达，增加了NF-κB的激活，并提高了促炎细胞因子的产生。这些发现为这些基因变异在干燥综合征发病机制中的功能意义提供了有力证据，并强调了CRISPR-Cas9技术在阐明自身免疫性疾病的遗传贡献方面的实用性。
