Dysregulated MicroRNA Involvement in Multiple Sclerosis by Induction of T Helper 17 Cell Differentiation

Abstract

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system. Growing evidence has proven that T helper 17 (Th17) cells are one of the regulators of neuroinflammation mechanisms in MS disease. Researchers have demonstrated that some microRNAs (miRNAs) are associated with disease activity and duration, even with different MS patterns. miRNAs regulate CD4⁺ T cells to differentiate toward various T cell subtypes including Th17 cells. In this review, we discuss the possible mechanisms of miRNAs in MS pathophysiology by regulating CD4⁺ T cell differentiation into Th17 cells, and potential miRNA targets for current disease-modifying treatments.

Keywords: T helper 17 cells; experimental autoimmune encephalomyelitis; microRNA; multiple sclerosis; treatment.

Figure 1

Mechanisms of specific microRNAs (miRNAs) in T helper 17 (Th17) cell differentiation and targets for current treatments. Most miRNAs promote Th17 cell differentiation and exacerbate multiple sclerosis and experimental autoimmune encephalomyelitis, while miRNA-15b, -20b, -26a, -30a, -132, and -146a show negative regulation of Th17 cell differentiation. The signal transducer and activator of transcription (STAT) 3-related orphan receptor (ROR) γt–interleukin (IL)-17 signaling pathway is downstream of most miRNAs.