Faculty of Health Science and Medicine, Population Health and Neuroimmunology Unit, Bond University, Robina, Queensland, Australia.
J Affect Disord. 2012 Dec 10;141(2-3):261-9. doi: 10.1016/j.jad.2012.03.037. Epub 2012 May 8.
Immune dysfunction associated with a disease often has a molecular basis. A novel group of molecules known as microRNAs (miRNAs) have been associated with suppression of translational processes involved in cellular development and proliferation, protein secretion, apoptosis, immune function and inflammatory processes. MicroRNAs may be implicated in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME), where immune function is impaired. The objective of this study was to determine the association between miRNAs in cytotoxic cells and CFS/ME.
Natural Killer (NK) and CD8(+)T cells were preferentially isolated from peripheral blood mononuclear cells from all participants (CFS/ME, n=28; mean age=41.8±9.6 years and controls, n=28; mean age=45.3±11.7 years), via negative cell enrichment. Following total RNA extraction and subsequent synthesis of cDNA, reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) was used to determine the expression levels of nineteen miRNAs.
There was a significant reduction in the expression levels of miR-21, in both the NK and CD8(+)T cells in the CFS/ME sufferers. Additionally, the expression of miR-17-5p, miR-10a, miR-103, miR-152, miR-146a, miR-106, miR-223 and miR-191 was significantly decreased in NK cells of CFS/ME patients in comparison to the non-fatigued controls.
The results from these investigations are not yet transferable into the clinical setting, further validatory studies are now required.
Collectively these miRNAs have been associated with apoptosis, cell cycle, development and immune function. Changes in miRNAs in cytotoxic cells may reduce the functional capacity of these cells and disrupt effective cytotoxic activity along with other immune functions in CFS/ME patients.
与疾病相关的免疫功能障碍通常具有分子基础。一组被称为 microRNAs(miRNAs)的新型分子与细胞发育和增殖、蛋白质分泌、细胞凋亡、免疫功能和炎症过程中涉及的翻译过程的抑制有关。microRNAs 可能与慢性疲劳综合征/肌痛性脑脊髓炎(CFS/ME)有关,其中免疫功能受损。本研究的目的是确定细胞毒性细胞中的 miRNAs 与 CFS/ME 之间的关联。
通过阴性细胞富集,从所有参与者(CFS/ME,n=28;平均年龄=41.8±9.6 岁和对照组,n=28;平均年龄=45.3±11.7 岁)的外周血单核细胞中优先分离自然杀伤(NK)和 CD8+T 细胞。提取总 RNA 并随后合成 cDNA 后,使用逆转录定量聚合酶链反应(RT-qPCR)来确定 19 种 miRNAs 的表达水平。
在 CFS/ME 患者的 NK 和 CD8+T 细胞中,miR-21 的表达水平均显著降低。此外,与非疲劳对照组相比,CFS/ME 患者的 NK 细胞中 miR-17-5p、miR-10a、miR-103、miR-152、miR-146a、miR-106、miR-223 和 miR-191 的表达也显著降低。
这些研究的结果尚未可转移到临床环境中,现在需要进一步的验证性研究。
这些 miRNAs 共同与细胞凋亡、细胞周期、发育和免疫功能有关。细胞毒性细胞中 miRNAs 的变化可能会降低这些细胞的功能能力,并破坏 CFS/ME 患者的有效细胞毒性活性和其他免疫功能。