Xu Bing, Liu Yuan, Chen Guangfeng, Jiang Ping, Qu Yuan, Wang Mengjie, Kao Xiliang
Department of Rheumatology, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.
The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China.
Autoimmunity. 2025 Dec;58(1):2448463. doi: 10.1080/08916934.2024.2448463. Epub 2025 Jan 1.
Systemic lupus erythematosus (SLE) is an autoimmune disease with complex clinical manifestations and no current cure. Alternative splicing (AS) plays a key role in SLE by regulating immune-related genes, but its genome-wide regulatory mechanisms remain unclear. To investigate the involvement of abnormal splicing regulators and AS events in the immune regulation of SLE. Transcriptome data from the SLE dataset GSE162828 were analyzed for differential gene expression and AS events using bioinformatics tools. Immune infiltration analysis was conducted with CIBERSORT, and co-expression of key splicing factors (SFs) and AS events was assessed using SUVA software. A total of 5144 differentially expressed genes and 73 SFs were identified. Significant immune cell differences were observed between SLE and controls, highlighting SFs such as HNRNPDL, RBM47, TIA1, SSB, and DHX15. Eighty-three AS events were identified, with IRF9 and PTPRC emerging as key regulatory events linked to SLE. Dysregulated SFs influence AS in immune-related genes, affecting immune cell composition and SLE progression. These findings offer potential new therapeutic targets for modulating the immune microenvironment in SLE.
系统性红斑狼疮（SLE）是一种临床表现复杂且目前无法治愈的自身免疫性疾病。可变剪接（AS）通过调节免疫相关基因在SLE中发挥关键作用，但其全基因组调控机制仍不清楚。为了研究异常剪接调节因子和AS事件在SLE免疫调节中的作用，利用生物信息学工具分析了SLE数据集GSE162828的转录组数据，以检测差异基因表达和AS事件。使用CIBERSORT进行免疫浸润分析，并使用SUVA软件评估关键剪接因子（SFs）与AS事件的共表达情况。共鉴定出5144个差异表达基因和73个SFs。观察到SLE患者与对照组之间存在显著的免疫细胞差异，突出了HNRNPDL、RBM47、TIA1、SSB和DHX15等SFs。鉴定出83个AS事件，其中IRF9和PTPRC成为与SLE相关的关键调控事件。失调的SFs影响免疫相关基因的AS，影响免疫细胞组成和SLE进展。这些发现为调节SLE免疫微环境提供了潜在的新治疗靶点。
