Lai N-S, Yu H-C, Huang K-Y, Tung C-H, Huang H-B, Lu M-C
1 Division of Allergy, Immunology and Rheumatology, Dalin Tzu Chi Hospital, Chiayi, Taiwan.
2 School of Medicine, Tzu Chi University, Hualien City, Taiwan.
Lupus. 2018 Aug;27(9):1499-1508. doi: 10.1177/0961203318778362. Epub 2018 May 31.
Objective To investigate whether the aberrant expression of non-coding RNAs (ncRNAs) in T cells from patients with systemic lupus erythematosus (SLE) could contribute to the pathogenesis of lupus. Methods Expression profiles of RNA transcripts in T cells from three patients with SLE and three controls were analyzed by microarray analysis. Potentially aberrant-expressed ncRNAs were validated using T cell samples from 23 patients with SLE and 17 controls. Transfection studies and microarray analyses were conducted to search for any gene expression that is regulated by specific ncRNAs. Results Initial analysis revealed differential expression of 18 ncRNAs in SLE T cells. After validation, decreased expression of H/ACA box small nucleolar RNA 12 (SNORA12) was confirmed in SLE T cells (0.69-fold, P = 0.007) compared with normal T cells, and its expression level was inversely associated with higher SLE disease activity scores. Jurkat cells transfected with a plasmid encoding SNORA12 showed increased expression of two genes and decreased expression of 15 genes in Jurkat cells. These changes of gene expression were significantly associated with the SLE pathway in the Kyoto Encyclopedia of Genes and Genomes map using microarray analysis. Overexpression of SNORA12 altered the expression of CD69, decreased the expression of histone cluster 1 H4 family member k (HIST1H4K), inhibited the secretion of interferon gamma and the expression of HIST1H4K was increased in SLE T cells. Conclusion Among the ncRNAs, we found that the expression level of SNORA12, which belongs to the family of small nucleolar RNAs, was lower in SLE T cells and affected T cell function. This novel finding suggests that aberrant-expressed snoRNAs lead to dysfunction of T cells and may be involved in the immunopathogenesis of SLE.
目的 研究系统性红斑狼疮（SLE）患者T细胞中非编码RNA（ncRNA）的异常表达是否有助于狼疮的发病机制。方法 通过微阵列分析对3例SLE患者和3例对照者T细胞中的RNA转录本表达谱进行分析。使用来自23例SLE患者和17例对照者的T细胞样本对潜在异常表达的ncRNA进行验证。进行转染研究和微阵列分析以寻找受特定ncRNA调控的任何基因表达。结果 初步分析显示SLE T细胞中有18种ncRNA表达存在差异。验证后，与正常T细胞相比，SLE T细胞中H/ACA盒小核仁RNA 12（SNORA12）的表达降低（0.69倍，P = 0.007），其表达水平与较高的SLE疾病活动评分呈负相关。用编码SNORA12的质粒转染的Jurkat细胞显示Jurkat细胞中有2个基因表达增加，15个基因表达降低。使用微阵列分析，这些基因表达变化与京都基因与基因组百科全书图谱中的SLE途径显著相关。SNORA12的过表达改变了CD69的表达，降低了组蛋白簇1 H4家族成员k（HIST1H4K）的表达，抑制了干扰素γ的分泌，并且SLE T细胞中HIST1H4K的表达增加。结论 在ncRNA中，我们发现属于小核仁RNA家族的SNORA12在SLE T细胞中的表达水平较低，并影响T细胞功能。这一新发现表明异常表达的小核仁RNA导致T细胞功能障碍，可能参与SLE的免疫发病机制。
