Aberrant expression of interleukin-23-regulated miRNAs in T cells from patients with ankylosing spondylitis

Arthritis Res Ther. 2018 Nov 21;20(1):259. doi: 10.1186/s13075-018-1754-1.

Abstract

Background: Interleukin (IL)-23 can facilitate the differentiation of IL-17-producing helper T cells (Th17). The IL-23/IL-17 axis is known to play a key role in the immunopathogenesis of ankylosing spondylitis (AS). We hypothesized that the expression of microRNAs (miRNAs, miRs) would be regulated by IL-23 and that these miRNAs could participate in the immunopathogenesis of AS.

Methods: Expression profiles of human miRNAs in K562 cells, cultured in the presence or absence of IL-23 for 3 days, were analyzed by microarray. Potentially aberrantly expressed miRNAs were validated using T-cell samples from 24 patients with AS and 16 control subjects. Next-generation sequencing (NGS) was conducted to search for gene expression and biological functions regulated by specific miRNAs in the IL-23-mediated signaling pathway.

Results: Initial analysis revealed that the expression levels of 12 miRNAs were significantly higher, whereas those of 4 miRNAs were significantly lower, in K562 cells after coculture with IL-23 for 3 days. Among these IL-23-regulated miRNAs, the expression levels of miR-29b-1-5p, miR-4449, miR-211-3p, miR-1914-3p, and miR-7114-5p were found to be higher in AS T cells. The transfection of miR-29b-1-5p mimic suppressed IL-23-mediated signal transducer and activator of transcription 3 (STAT3) phosphorylation in K562 cells. After NGS analysis and validation, we found that miR-29b-1-5p upregulated the expression of angiogenin, which was also upregulated in K562 cells after coculture with IL-23. Increased expression of miR-29b-1-5p or miR-211-3p could enhance interferon-γ expression.

Conclusions: Among the miRNAs regulated by IL-23, expression levels of five miRNAs were increased in T cells from patients with AS. The transfection of miR-29b-1-5p mimic could inhibit the IL-23-mediated STAT3 phosphorylation and might play a role in negative feedback control in the immunopathogenesis of AS.

Keywords: Angiogenin; Ankylosing spondylitis; IL-23; MicroRNAs; STAT3; T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Gene Expression Regulation
  • Humans
  • Interleukin-23 / biosynthesis*
  • Interleukin-23 / genetics
  • K562 Cells
  • Male
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Middle Aged
  • Receptors, Interleukin / biosynthesis*
  • Receptors, Interleukin / genetics
  • Spondylitis, Ankylosing / diagnosis
  • Spondylitis, Ankylosing / genetics
  • Spondylitis, Ankylosing / metabolism*
  • T-Lymphocytes / metabolism*

Substances

  • IL23R protein, human
  • Interleukin-23
  • MicroRNAs
  • Receptors, Interleukin