Decreased microRNA miR-181c expression in peripheral blood mononuclear cells correlates with elevated serum levels of IL-7 and IL-17 in patients with myasthenia gravis

Clin Exp Med. 2016 Aug;16(3):413-21. doi: 10.1007/s10238-015-0358-1. Epub 2015 May 12.

Abstract

miR-181c is a newly identified negative regulator of immune cell activation. In this study, we aimed to investigate the expression and functional role of miR-181c in myasthenia gravis (MG). miR-181c showed significant downregulation in peripheral blood mononuclear cells (PBMCs) from MG patients compared with healthy controls, with lower expression in generalized patients than in ocular ones. MG patients also had increased serum IL-7 and IL-17 levels. Additionally, serum IL-7 level presents a positive correlation with the serum IL-17 level. miR-181c levels were negatively correlated with serum levels of IL-7 and IL-17 in either generalized patients or ocular patients. A luciferase reporter assay revealed that miR-181c could directly bind to the 3'-UTR of interleukin-7. Forced expression of miR-181c led to decreased IL-7 and IL-17 release in cultured PBMCs, while depletion of miR-181c increased the secretion of these two proinflammatory cytokines. The results from our study suggested for the first time that miR-181c was able to negatively regulate the production of proinflammatory cytokines IL-7 and IL-17 in MG patients, and it is a novel potential therapeutic target for MG.

Keywords: IL-17; IL-7; MiR-181c; MicroRNAs; Myasthenia gravis.

MeSH terms

  • Adult
  • Aged
  • Down-Regulation
  • Female
  • Humans
  • Interleukin-17 / blood*
  • Interleukin-7 / blood*
  • Leukocytes, Mononuclear / chemistry*
  • Male
  • MicroRNAs / analysis*
  • Middle Aged
  • Myasthenia Gravis / pathology*
  • Serum / chemistry*

Substances

  • IL17A protein, human
  • IL7 protein, human
  • Interleukin-17
  • Interleukin-7
  • MIrn181 microRNA, human
  • MicroRNAs