MicroRNA let‐7e is associated with the pathogenesis of experimental autoimmune encephalomyelitis

Abstract

MicroRNAs (miRNAs) play important roles in the regulation of immune responses. There is evidence that miRNAs also participate in the pathogenesis of multiple sclerosis (MS), but how the miRNAs regulate the pathogenesis of MS is still under investigation. The identification of new members of the miRNA family associated with the pathogenesis of MS could facilitate early diagnosis and treatment. Here we show that the level of miRNA let-7e is significantly upregulated in experimental autoimmune encephalomyelitis (EAE), an animal model of MS using miRNA array and quantitative real-time PCR. The expression of let-7e was mainly in CD4+ T cells and infiltrated mononuclear cells of central nervous system, and highly correlated with the development of EAE. We found that let-7e silencing in vivo inhibited encephalitogenic Th1 and Th17 cells and attenuated EAE, with reciprocal increase of Th2 cells; overexpression of let-7e enhanced Th1 and Th17 cells and aggravated EAE. We also identified IL-10 as one of the functional targets of let-7e. Together, we propose that let-7e is a new miRNA involved in the regulation of encephalitogenic T-cell differentiation and the pathogenesis of EAE.

MicroRNA‐132 suppresses autoimmune encephalomyelitis by inducing cholinergic anti‐inflammation: A new Ahr‐based exploration

“…It has been demonstrated that Ahr plays a prominent role in EAE pathogenesis, and the activation of Ahr by TCDD ameliorates disease symptoms [5]. Recently, it has been revealed that several miRNAs are associated with the development of MS [28,29] and targeting specific miRNAs showed therapeutic potential in EAE [11][12][13]. However, the interaction between Ahr and miRNAs in EAE is yet unexplored.…”

“…Recent in vivo studies have revealed the biological significance of certain miRNAs in autoimmune inflammation. MiR-155, miR-326, and let-7e are upregulated in EAE mice; deletion or silencing these miRNAs results in defects in the inflammatory T cells and attenuates disease symptoms [11][12][13]. Mice overexpressing miR-17-92 cluster in lymphocytes develop autoimmune conditions [14].…”

Increases of microRNA let-7e in peripheral blood mononuclear cells in Hashimoto’s disease

“…Generally, IL-10 is classified as a Th2 cytokine, and it has anti-inflammatory functions and suppresses Th1 cytokine production [22,23]. The expression level of let-7e was shown to be increased in infiltrated mononuclear cells in the brain and spinal cord of experimental autoimmune encephalomyelitis (EAE) mice [21]. It was also thought that let-7e modulates the balance of Th1/Th2 cytokines and the development of EAE by targeting IL-10 genes [21].…”

“…The expression level of let-7e was shown to be increased in infiltrated mononuclear cells in the brain and spinal cord of experimental autoimmune encephalomyelitis (EAE) mice [21]. It was also thought that let-7e modulates the balance of Th1/Th2 cytokines and the development of EAE by targeting IL-10 genes [21]. Therefore, let-7e may be a principal regulator that controls the expression of IL-10 in various physiological and pathological processes, including autoimmune dis-accordance with the manufacturer's protocol.…”

“…Recently, let-7e was shown to directly target the 3′ untranslated region of interleukin (IL)-10 genes, leading to the repression of those genes [19][20][21]. Generally, IL-10 is classified as a Th2 cytokine, and it has anti-inflammatory functions and suppresses Th1 cytokine production [22,23].…”