Unraveling the Equine Lymphocyte Proteome: Differential Septin 7 Expression Associates with Immune Cells in Equine Recurrent Uveitis

Equine recurrent uveitis is a spontaneous, lymphocyte-driven autoimmune disease. It affects horses worldwide and presents with painful remitting-relapsing inflammatory attacks of inner eye structures eventually leading to blindness. Since lymphocytes are the key players in equine recurrent uveitis, we were interested in potential changes of their protein repertoire which may be involved in disease pathogenesis. To create a reference for differential proteome analysis, we first unraveled the equine lymphocyte proteome by two-dimensional sodium dodecyl sulfate - polyacrylamide gel electrophoresis and subsequently identified 352 protein spots. Next, we compared lymphocytes from ERU cases and healthy horses with a two-dimensional fluorescence difference in gel electrophoresis approach. With this technique, we identified seven differentially expressed proteins between conditions. One of the significantly lower expressed candidates, septin 7, plays a role in regulation of cell shape, motility and migration. Further analyses revealed T cells as the main cell type with decreased septin 7 abundance in equine recurrent uveitis. These findings point to a possible pathogenetic role of septin 7 in this sight-threatening disease.

马复发性葡萄膜炎（Equine recurrent uveitis）是一种自发性、淋巴细胞介导的自身免疫性疾病，在全球范围内均可感染马匹，表现为眼部内层结构反复发作的疼痛性炎症发作，最终可导致失明。鉴于淋巴细胞是马复发性葡萄膜炎的核心致病因子，我们着手探究其蛋白质组的潜在变化——这些变化可能与疾病发病机制相关。为构建差异蛋白质组分析的参照数据集，我们首先通过二维十二烷基硫酸钠-聚丙烯酰胺凝胶电泳解析马淋巴细胞的蛋白质组，随后共鉴定出352个蛋白质斑点。接下来，我们采用二维荧光差异凝胶电泳技术，对比了马复发性葡萄膜炎（ERU）病例与健康马的淋巴细胞。通过该技术，我们鉴定出两组间共7个差异表达蛋白质。其中一个显著低表达的候选蛋白为septin 7（septin 7），该蛋白参与调控细胞形态、运动及迁移能力。进一步分析显示，在马复发性葡萄膜炎病例中，T细胞是septin 7表达丰度降低的主要细胞类型。上述研究结果表明，septin 7可能在这种威胁视力的疾病中发挥致病作用。