Epithelial cell-derived micro RNA-146a generates interleukin-10-producing monocytes to inhibit nasal allergy

Sci Rep. 2015 Nov 3:5:15937. doi: 10.1038/srep15937.

Abstract

The aberrant immunity plays an important role in the pathogenesis of allergic diseases. Micro RNAs (miR) are involved in regulating the immunity in the body. This study aims to test a hypothesis that miR-146a induces the expression of interleukin (IL)-10 in monocytes (Mos). In this study, the levels of miR-146a were determined by real time RT-PCR. The IL-10(+) Mos were evaluated by flow cytometry. The miR-146a-laden exosomes were generated with RPMI2650 cells (an airway epithelial cell line). An allergic rhinitis mouse model was developed. The results showed that nasal epithelial cells expressed miR-146a, which was markedly lower in the nasal epithelial cells of patients with nasal allergy than that in healthy controls. Exposure to T helper (Th)2 cytokines suppressed the levels of miR-146a in the nasal epithelial cells. The nasal epithelial cell-derived miR-146a up regulated the expression of IL-10 in Mos. The inducible IL-10(+) Mos showed an immune suppressor effect on the activities of CD4(+) effector T cells and the Th2 polarization in a mouse model of allergic rhinitis. In summary, nasal epithelial cells express miR-146a, the latter is capable of inducing IL-10 expression in Mos, which suppress allergic reactions in the mouse nasal mucosa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer / methods
  • Animals
  • Blotting, Western
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Cytokines / immunology
  • Cytokines / metabolism
  • Epithelial Cells / immunology*
  • Epithelial Cells / metabolism
  • Exosomes / immunology
  • Exosomes / metabolism
  • Humans
  • Interleukin-10 / biosynthesis
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology*
  • Male
  • Mice, Inbred BALB C
  • Mice, Knockout
  • MicroRNAs / genetics
  • MicroRNAs / immunology*
  • Monocytes / immunology*
  • Monocytes / metabolism
  • Monocytes / transplantation
  • Nasal Mucosa / immunology
  • Nasal Mucosa / metabolism
  • Nasal Mucosa / pathology
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • Rhinitis, Allergic / genetics
  • Rhinitis, Allergic / immunology*
  • Rhinitis, Allergic / metabolism
  • Th2 Cells / immunology
  • Th2 Cells / metabolism

Substances

  • Cytokines
  • IL10 protein, human
  • MIRN146 microRNA, human
  • MicroRNAs
  • Interleukin-10