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

Chen Chen,Yifan Zhou,Lisheng Peng,Yaping Yan,Jingqi Wang,Wei Qiu

doi:10.3389/fimmu.2018.01256

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.

Highlights

Multiple sclerosis (MS) is an autoimmune disease characterized by chronic inflammatory demyelination in the central nervous system (CNS), which can result in cognitive decline and permanent disability among young adults
The T helper 17 (Th17) cell lineage is characterized by expression of RORγ and STAT3, both of which are the basis for the cytokine profile, including IL-6, IL-12, IL-17, IL-22, and tumor necrosis factor (TNF), which mediate tissue inflammation
A recent study of miRNAs showed that miR-17 and miR-29 are upregulated in CD4+ T cells during relapse and downregulated after natalizumab treatment [67,68,69]. miR-17 is a regulator of genes involved in T cell activation [25] and promotes Th17 cell differentiation by inhibiting Ikaros family zinc finger 4 (IKZF4) [55]

Summary

INTRODUCTION

Multiple sclerosis (MS) is an autoimmune disease characterized by chronic inflammatory demyelination in the central nervous system (CNS), which can result in cognitive decline and permanent disability among young adults. IL-17+-producing T cells were elevated in the active rather than in inactive areas of MS lesions, and significantly higher densities presented within acute lesions and active borders of chronic active lesions than in normal-appearing white matter [3]. Cytokines produced by Th17 cells are most likely to be critical pathological factors in autoimmune diseases, MS. Th17 cell clones generated from the CSF and peripheral blood of MS patients expressed high levels of activation markers, adhesion molecules, and co-stimulatory molecules than Th1 clones [10]. The Th17 cell lineage is characterized by expression of RORγ and STAT3, both of which are the basis for the cytokine profile, including IL-6, IL-12, IL-17, IL-22, and tumor necrosis factor (TNF), which mediate tissue inflammation. Th17 cell-mediated pathology [16]; the other subset was generated by IL-1β, IL-6, IL-23, and TGF-β, which was considered as pathogenic Th17 cells [17]

DYSREGULATED miRNAs IN MS

Upregulated depends on aryl hydrocarbon receptor under

MODIFYING TREATMENTS

ADVANCES IN miRNA TECHNIQUES

Findings

PERSPECTIVES AND CONCLUSION