State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases; Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Department of Conservative Dentistry, Division of Biomaterials and Engineering, Showa University School of Dentistry, Tokyo, Japan.
Front Immunol. 2021 Apr 14;12:624614. doi: 10.3389/fimmu.2021.624614. eCollection 2021.
Primary Sjogren's syndrome (pSS) is a chronic progressive autoimmune disease with clinical phenotypic "Sicca symptoms". In some cases, the diagnosis of pSS is delayed by 6-7 years due to the inefficient differential diagnosis of pSS and non-SS "Sicca". This study aimed to investigate the difference between these two diseases, and in particular, their immunopathogenesis. Based on their gene expression profiles, we systematically defined for the first time the predicted disease-specific immune infiltration pattern of patients with pSS differentiated from normal donors and patients with non-SS "Sicca". We found that it was characterized by the aberrant abundance and interaction of tissue-infiltrated immune cells, such as a notable shift in the subpopulation of six immune cells and the perturbed abundance of nine subpopulations, such as CD4+ memory, CD8+ T-cells and gamma delta T-cells. In addition, we identified essential genes, particularly long non-coding RNAs (lncRNAs), as the potential mechanisms linked to this predicted pattern reprogramming. Fourteen lncRNAs were identified as the potential regulators associated with the pSS-specific immune infiltration pattern in a synergistic manner, among which the lncRNA was highly relevant to chemokine signaling pathways. In conclusion, aberrant predicted disease-specific immune infiltration patterns and relevant genes revealed the immunopathogenesis of pSS and provided some clues for the immunotherapy by targeting specific immune cells and genes.
原发性干燥综合征(pSS)是一种慢性进行性自身免疫性疾病,具有临床表型“干燥症状”。由于 pSS 与非 SS“干燥”的鉴别诊断效率低下,导致该病的诊断延迟了 6-7 年。本研究旨在探讨这两种疾病的差异,特别是它们的免疫发病机制。基于基因表达谱,我们首次系统地定义了从正常供体和非 SS“干燥”患者中区分 pSS 患者的预测疾病特异性免疫浸润模式。我们发现,其特征是组织浸润免疫细胞的异常丰度和相互作用,例如六种免疫细胞亚群的显著偏移以及九个亚群的丰度紊乱,如 CD4+记忆细胞、CD8+T 细胞和γδ T 细胞。此外,我们确定了关键基因,特别是长非编码 RNA(lncRNA),作为与这种预测模式重编程相关的潜在机制。鉴定出 14 个 lncRNA 作为与 pSS 特异性免疫浸润模式相关的潜在调节剂,以协同方式发挥作用,其中 lncRNA 与趋化因子信号通路高度相关。总之,异常的预测疾病特异性免疫浸润模式和相关基因揭示了 pSS 的免疫发病机制,并为针对特定免疫细胞和基因的免疫治疗提供了一些线索。