Liao Zhengyue, He Liying, Fu Jiaojiao, Zhou Xiaotong, Li Yong, He Jing, Liu Yixin, Guo Jinlin, Liu Sijing
College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, China; Chongqing Key Laboratory of Sichuan-Chongqing Co-construction for Diagnosis and Treatment of Infectious Diseases Integrated Traditional Chinese and Western Medicine, Chengdu, China.
State Key Laboratory of Southwestern Chinese Medicine Resources, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Biomol Biomed. 2025 Jan 14;25(2):406-424. doi: 10.17305/bb.2024.10450.
Lupus nephritis (LN) is an autoimmune disease that rapidly progresses as a secondary consequence of systemic lupus erythematosus (SLE) and has a very poor prognosis. Therefore, this study aimed to identify characteristics of immune cell infiltration and investigate potential therapeutic targets using bioinformatics methods and the Murphy Roths Large/lymphoproliferation (MRL/lpr) mouse model. In this study, a total of 2,810 differentially expressed genes (DEGs) were identified, which were primarily enriched in inflammatory and immune regulation pathways. From these DEGs, 226 immune-related genes (IRGs) were also identified. The single-sample gene set enrichment analysis (ssGSEA) revealed that patients with LN had increased infiltration of effector memory CD4+ T cells, effector memory CD8+ T cells, gamma delta T cells, myeloid-derived suppressor cells (MDSC), follicular helper T cells, Th1 cells, and Th2 cells, and this was closely correlated with the DEG-IRGs. Furthermore, the potential therapeutic biomarkers, CD244, S100 calcium binding protein P (S100P), and vascular endothelial growth factor C (VEGFC), were identified by Random Forest Approach (RFA), which were validated in LN mice. These findings provide new evidence and insights for further research on diagnosis and treatment of LN by identifying critical genes and their associations with immune infiltration.
狼疮性肾炎(LN)是一种自身免疫性疾病,作为系统性红斑狼疮(SLE)的继发后果会迅速进展,预后很差。因此,本研究旨在利用生物信息学方法和墨菲罗斯大/淋巴细胞增殖(MRL/lpr)小鼠模型来识别免疫细胞浸润的特征并研究潜在的治疗靶点。在本研究中,共鉴定出2810个差异表达基因(DEG),这些基因主要富集于炎症和免疫调节途径。从这些DEG中,还鉴定出226个免疫相关基因(IRG)。单样本基因集富集分析(ssGSEA)显示,LN患者的效应记忆CD4+ T细胞、效应记忆CD8+ T细胞、γδ T细胞、髓系来源的抑制细胞(MDSC)、滤泡辅助性T细胞、Th1细胞和Th2细胞浸润增加,且这与DEG-IRG密切相关。此外,通过随机森林方法(RFA)鉴定出潜在的治疗生物标志物CD244、S100钙结合蛋白P(S100P)和血管内皮生长因子C(VEGFC),并在LN小鼠中得到验证。这些发现通过识别关键基因及其与免疫浸润的关联,为LN的诊断和治疗进一步研究提供了新的证据和见解。