Role of miR-146a in Enforcing Effect of Specific Immunotherapy on Allergic Rhinitis

Immunol Invest. 2016;45(1):1-10. doi: 10.3109/08820139.2015.1085390. Epub 2015 Dec 23.

Abstract

Allergic rhinitis (AR) is one of the common disorders in airway allergic inflammation. The pathogenesis of AR is unclear. It is accepted that immune deregulation is associated with the pathogenesis of AR. Recent reports suggest that a large number of micro RNAs (miR) can regulate immune functions. This study aims to investigate the role of miR-146a in an enforcing immunotherapy of AR. In this study, a mouse AR model was created. The levels of miR-146a in the mouse nasal mucosa were assessed by real time RT-PCR. A specific immunotherapy was performed in AR mice. The results showed that the AR mice had an AR-like inflammation in the nasal mucosa. Compared with naïve mice, markedly lower levels of miR-146a were detected in AR mice. The co-administration with miR-146a significantly enforced the effect of ovalbumin (OVA)-specific immunotherapy on inhibition of AR inflammation in the nasal mucosa. Further analysis showed that miR-146a induced transforming growth factor-β in dendritic cells; the latter induced naïve CD4(+) T cells to differentiate into regulatory T cells. In conclusion, miR-146a can enforce OVA-specific immunotherapy via inducing antigen-specific regulatory T cells. miR-146a may have therapeutic potential to be used in the immunotherapy of allergic diseases.

Keywords: Allergy; immunotherapy; micro RNA; nasal mucosa; vaccine.

MeSH terms

  • Animals
  • Case-Control Studies
  • Cytokines / metabolism
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Disease Models, Animal
  • Epitopes, T-Lymphocyte / immunology
  • Gene Expression
  • Humans
  • Immunoglobulin E / blood
  • Immunoglobulin E / immunology
  • Immunotherapy*
  • Immunotherapy, Adoptive
  • Lymphocyte Count
  • Male
  • Mice
  • MicroRNAs / genetics*
  • Nanoparticles
  • Nasal Mucosa / cytology
  • Nasal Mucosa / immunology
  • Nasal Mucosa / metabolism
  • Ovalbumin / immunology
  • Rhinitis, Allergic / diagnosis
  • Rhinitis, Allergic / genetics*
  • Rhinitis, Allergic / immunology*
  • Rhinitis, Allergic / metabolism
  • Rhinitis, Allergic / therapy
  • T-Cell Antigen Receptor Specificity / immunology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism
  • Vaccines / immunology

Substances

  • Cytokines
  • Epitopes, T-Lymphocyte
  • MicroRNAs
  • Mirn146 microRNA, mouse
  • Transforming Growth Factor beta
  • Vaccines
  • Immunoglobulin E
  • Ovalbumin