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

Abstract

BackgroundInterleukin (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.MethodsExpression 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.ResultsInitial 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.ConclusionsAmong 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.

Analysis of genetically independent phenotypes identifies shared genetic factors associated with chronic musculoskeletal pain conditions

“…Lead SNP rs73581580 is located in the intron of the EXD3 gene, an ortholog of C. elegans mut-7 gene required for transposon silencing and RNA interference in that organism. Nevertheless, results from other studies suggest four genes with more plausible effects on chronic musculoskeletal pain (MIR7114 35 , NOXA1 36 , NSMF 37,38 , and GRIN1 39 , Supplementary Data 5).…”

The Neat Dance of COVID-19: NEAT1, DANCR, and Co-Modulated Cholinergic RNAs Link to Inflammation

“…DANCR is notably active in lymphoid organs and T cell differentiation and presents massive increases following influenza vaccination ( 105 , 106 ). Compatible with a regulatory role for DANCR in SARS-CoV-2-generated lung infection, DANCR shares a genomic locus with miR-4449, which is upregulated in airway epithelial cells under respiratory syncytial virus (RSV) infection ( 107 ), and is dysregulated in lymphocytes of multiple myeloma and ankylosing spondylitis patients ( 108 , 109 ). Correspondingly, we identified DANCR as prominently reduced under SARS-CoV-2 infection, together with the lncRNA NEAT1 which controls RNA-regulating processes via forming the non-membranous organelle of the nuclear paraspeckles.…”

Prostaglandin receptor EP4 expression by Th17 cells is associated with high disease activity in ankylosing spondylitis

“…IL-23 is known to be implicated in the maintenance of the Th17 lineage [58]. In T cells from patients with AS, the expression levels of IL-23-regulated miRNAs are elevated [59]. In recent years, IL-23-targeting antibodies have been evaluated for the treatment of AS [60,61].…”