Chen Ji-Qing, Papp Gábor, Póliska Szilárd, Szabó Krisztina, Tarr Tünde, Bálint Bálint László, Szodoray Péter, Zeher Margit
Division of Clinical Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Genomic Medicine and Bioinformatic Core Facility, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
PLoS One. 2017 Mar 24;12(3):e0174585. doi: 10.1371/journal.pone.0174585. eCollection 2017.
The discovery of microRNAs (miRNAs) and their critical role in genetic control opened new avenues in understanding of various biological processes including immune cell lineage commitment, differentiation, proliferation and apoptosis. However, a given miRNA may have hundreds of different mRNA targets and a target might be regulated by multiple miRNAs, thus the characterisation of dysregulated miRNA expression profiles could give a better insight into the development of immunological disturbances in autoimmune diseases. The aim of our study was to examine the changes in miRNA expression profiles in patients with systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS). Eight SLE patients, 8 pSS patients and 7 healthy subjects were enrolled in the investigation. MiRNAs were isolated from peripheral blood mononuclear cells, and expression patterns were determined with Illumina next-generation sequencing technology. Since the immunopathogenesis of pSS and SLE encompasses pronounced B cell hyperactivity along with specific autoantibody production, we paid a special attention on the association between miRNA expression levels and altered peripheral B cell distribution. In SLE patients 135, while in pSS patients 26 miRNAs showed altered expression. Interestingly, the 25 miRNAs including miR-146a, miR-16 and miR-21, which were over-expressed in pSS patients, were found to be elevated in SLE group, as well. On the contrary, we observed the down-regulation of miR-150-5p, which is a novel and unique finding in pSS. Levels of several miRNAs over-expressed in SLE, were not changed in pSS, such as miR-148a-3p, miR-152, miR-155, miR-223, miR-224, miR-326 and miR-342. Expression levels of miR-223-5p, miR-150-5p, miR-155-5p and miR-342-3p, which miRNAs are potentially linked to B cell functions, showed associations with the B cell proportions within peripheral blood mononuclear cells. The observed differences in miRNA expression profiles and the better understanding of immune regulatory mechanisms of miRNAs may help to elucidate the pathogenesis of SLE and pSS.
微小RNA(miRNA)的发现及其在基因调控中的关键作用为理解包括免疫细胞谱系定向、分化、增殖和凋亡在内的各种生物学过程开辟了新途径。然而,一个特定的miRNA可能有数百个不同的mRNA靶标,且一个靶标可能受多个miRNA调控,因此对失调的miRNA表达谱进行表征可能有助于更深入了解自身免疫性疾病中免疫紊乱的发展。我们研究的目的是检测系统性红斑狼疮(SLE)和原发性干燥综合征(pSS)患者miRNA表达谱的变化。8例SLE患者、8例pSS患者和7名健康受试者参与了该研究。从外周血单核细胞中分离miRNA,并用Illumina下一代测序技术确定其表达模式。由于pSS和SLE的免疫发病机制包括明显的B细胞高活性以及特异性自身抗体的产生,我们特别关注miRNA表达水平与外周血B细胞分布改变之间的关联。在SLE患者中有135个,而在pSS患者中有26个miRNA显示表达改变。有趣的是,包括miR-146a、miR-16和miR-21等25个在pSS患者中过表达的miRNA在SLE组中也被发现升高。相反,我们观察到miR-150-5p的下调,这在pSS中是一个新的独特发现。在SLE中过表达的几个miRNA的水平在pSS中没有变化,如miR-148a-3p、miR-152、miR-155、miR-223、miR-224、miR-326和miR-342。miR-223-5p、miR-150-5p、miR-155-5p和miR-342-3p的表达水平,这些miRNA可能与B细胞功能相关,显示出与外周血单核细胞内B细胞比例的关联。观察到的miRNA表达谱差异以及对miRNA免疫调节机制的更好理解可能有助于阐明SLE和pSS的发病机制。