Department of Immunology, Institute for Biological Research "SinišaStanković", University of Belgrade, Serbia.
Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Serbia.
Biomed Pharmacother. 2015 Aug;74:206-10. doi: 10.1016/j.biopha.2015.08.011. Epub 2015 Aug 15.
MicroRNAs (miR) are small non-coding RNAs involved in the immune response regulation. miR-155 has been attributed a major pro-inflammatory role in the pathogenesis of multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). Here, a role of miR-155 in re-activation of encephalitogenic CD4(+) T cells was investigated. Dark Agouti rats were immunized with myelin basic protein (MBP) emulsified in complete Freund's adjuvant. CD4(+) T cells were purified from draining lymph node cells (DLNC) obtained in the inductive phase and from spinal cord immune cells (SCIC) isolated at the peak of EAE. CD4(+) T cells obtained from SCIC (i.e., in vivo re-activated cells) had markedly higher expression of miR-155 in comparison to those purified from DLNC (not re-activated). Likewise, in vitro re-activation of DLNC with MBP led to increase in miR-155 expression. Further, DLNC and DLNC CD4(+) T cells were transfected with an inhibitor of miR-155 during in vitro re-activation. As a result, expression of important CD4(+) T cell effector cytokines IFN-γ and IL-17, but not of regulatory cytokines IL-10 and TGF-β, was reduced. These results imply that miR-155 supports re-activation of encephalitogenic CD4(+) T cells. Our results contribute to a view that miR-155 might be a valuable target in multiple sclerosis therapy.
微小 RNA（miR）是参与免疫反应调节的小非编码 RNA。miR-155 在多发性硬化症及其动物模型实验性自身免疫性脑脊髓炎（EAE）的发病机制中被认为具有主要的促炎作用。在这里，研究了 miR-155 在重新激活致脑炎 CD4(+) T 细胞中的作用。用髓鞘碱性蛋白（MBP）乳化在完全弗氏佐剂中对深褐色大鼠进行免疫接种。从诱导期获得的引流淋巴结细胞（DLNC）和 EAE 高峰期分离的脊髓免疫细胞（SCIC）中纯化 CD4(+) T 细胞。与从 DLNC 中纯化的（未重新激活的）相比，从 SCIC 中获得的 CD4(+) T 细胞（即体内重新激活的细胞）中 miR-155 的表达明显更高。同样，用 MBP 体外重新激活 DLNC 会导致 miR-155 表达增加。此外，在体外重新激活 DLNC 期间，用 miR-155 的抑制剂转染 DLNC 和 DLNC CD4(+) T 细胞。结果，重要的 CD4(+) T 细胞效应细胞因子 IFN-γ 和 IL-17 的表达减少，但调节细胞因子 IL-10 和 TGF-β 的表达没有减少。这些结果表明，miR-155 支持致脑炎 CD4(+) T 细胞的重新激活。我们的研究结果表明，miR-155 可能是多发性硬化症治疗的一个有价值的靶点。
