Institute of Chemical Biology, Fundamental Medicine of the Siberian Division of Russian Academy of Sciences, Lavrentiev Ave. 8, Novosibirsk 630090, Russia.
Int J Mol Sci. 2023 Feb 23;24(5):4433. doi: 10.3390/ijms24054433.
It was shown that the spontaneous development of experimental encephalomyelitis (EAE) in C57BL/6 mice occurs due to changes in the profile of bone marrow stem cells differentiation. This leads to the appearance of lymphocytes producing antibodies-abzymes that hydrolyze DNA, myelin basic protein (MBP), and histones. The activity of abzymes in the hydrolysis of these auto-antigens slowly but constantly increases during the spontaneous development of EAE. Treatment of mice with myelin oligodendrocyte glycoprotein (MOG) leads to a sharp increase in the activity of these abzymes with their maximum at 20 days (acute phase) after immunization. In this work, we analyzed changes in the activity of IgG-abzymes hydrolyzing (pA), (pC), (pU), and six miRNAs (miR-9-5p, miR-219a-5p, miR-326, miR-155-5p, miR-21-3p, and miR-146a-3p) before and after mice immunization with MOG. Unlike abzymes hydrolyzing DNA, MBP, and histones, the spontaneous development of EAE leads not to an increase but to a permanent decrease of IgGs activity of hydrolysis of RNA-substrates. Treatment of mice with MOG resulted in a sharp but transient increase in the activity of antibodies by day 7 (onset of the disease), followed by a sharp decrease in activity 20-40 days after immunization. A significant difference in the production of abzymes against DNA, MBP, and histones before and after mice immunization with MOG with those against RNAs may be since the expression of many miRNAs decreased with age. This can lead to a decrease in the production of antibodies and abzymes that hydrolyze miRNAs with age mice.
研究表明,C57BL/6 小鼠实验性脑脊髓炎(EAE)的自发发展是由于骨髓干细胞分化谱的变化引起的。这导致产生抗体-abzymes 的淋巴细胞出现,这些 abzymes 可以水解 DNA、髓鞘碱性蛋白(MBP)和组蛋白。在 EAE 的自发发展过程中,这些 abzymes 对这些自身抗原的水解活性缓慢但持续增加。用髓鞘少突胶质细胞糖蛋白(MOG)治疗小鼠会导致这些 abzymes 的活性急剧增加,在免疫后 20 天(急性期)达到最大值。在这项工作中,我们分析了 MOG 免疫前后 IgG-abzymes 水解(pA)、(pC)、(pU)和 6 种 miRNA(miR-9-5p、miR-219a-5p、miR-326、miR-155-5p、miR-21-3p 和 miR-146a-3p)活性的变化。与水解 DNA、MBP 和组蛋白的 abzymes 不同,EAE 的自发发展不会导致 RNA 底物水解的 IgG 活性增加,而是导致持续减少。用 MOG 治疗小鼠会导致第 7 天(疾病发作)抗体活性急剧增加,然后在免疫后 20-40 天活性急剧下降。MOG 免疫前后针对 DNA、MBP 和组蛋白的 abzymes 的产生与针对 RNA 的 abzymes 的产生之间存在显著差异,这可能是由于许多 miRNA 的表达随年龄而降低。这可能导致随年龄增长,水解 miRNA 的抗体和 abzymes 的产生减少。