IgG4相关性疾病和原发性干燥综合征相关细胞因子谱的对比

Comparison of cytokine profiles associated with IgG4-related disease and primary Sj gren syndrome

目的:从分子水平探讨IgG4相关性疾病(IgG4-RD)和原发性干燥综合征(pSS)的相关细胞因子特征。方法:获得了17个小唾液腺(9个来自pSS患者,8个来自非pSS患者作为对照)、7个颌下腺(4个来自IgG4-RD患者,3个来自切除的颌下腺肿瘤周围的肉眼正常组织作为对照)的样本RNA-Seq数据,分析IgG4-RD和pSS来源样品中的差异表达基因和富集途径,以揭示这两种疾病的免疫炎症特征。结果:尽管三级淋巴结构(TLS)相关细胞因子(例如CXCL13、CCL19等)的表达显著增加,但对于受累组织的先天免疫反应特征,在IgG4-RD中观察到更显著成纤维细胞相关细胞因子及其受体的表达,巨噬细胞和中性粒细胞相关的细胞因子及其受体在pSS中有更为显著的表达。此外,IgG4-RD受累唾液腺中经典信号通路的富集模式也与pSS不同:在IgG4-RD中,JAK-STAT信号通路、NF-κB信号通路显著富集,而在pSS中,与细胞趋化性相关通路显著富集。结论:在IgG4-RD和pSS之间的转录水平上,相关细胞因子间有不同的分子和生物过程模式,这可能指导其后续的机制研究和药物靶点选择。

Objective:To investigate the immunoinflammatory characteristics of IgG4-related disease(IgG4-RD)and primary Sj gren syndrome(pSS)at molecular level.Methods:RNA-Seq data were obtained for a number of samples from 17 minor salivary glands(9 from pSS patients and 8 from non-pSS patients as controls),and 7 submandibular glands(4 from IgG4-RD patients and 3 from resected submandibular gland tumors surrounded by meaty,normal tissues as controls),and were analyzed for differentially expressed genes and enriched pathways in the samples of IgG4-RD and pSS origin in order to shed light on the immune-inflammatory features of the two distinct diseases.Results:Despite a significant increase in the expression of tertiary lymphoid structure(TLS)-associated cytokines(e.g.,CXCL13,CCL19,etc.),for the innate immune response characteristic of the involved tissues,more significant fibroblast related cytokines and their receptors were observed in IgG4-RD,whereas macrophage and neutrophil related cytokines and their receptors are more significantly expressed in pSS.In the salivary glands of IgG4-RD involvement,the pattern of enrichment of classical signaling pathways was also different from that of pSS:JAK-STAT signaling pathway and NF-κB signaling pathway were significantly enriched in IgG4-RD,whereas pathways related to cellular chemotaxis were significantly enriched in pSS.Conclusion:Different patterns of molecular and biological processes were observed in the related cytokines at the transcriptional level between IgG4-RD and pSS,which may guide their subsequent mechanistic studies and drug target selection.