Long non-coding RNA FOXD3-AS1 regulates the expression and secretion of IL-25 in nasal epithelial cells to inhibit Th2 type immunoreaction in allergic rhinitis

Mol Cell Biochem. 2020 Oct;473(1-2):239-246. doi: 10.1007/s11010-020-03825-4. Epub 2020 Jul 15.

Abstract

Long non-coding RNA FOXD3-AS1 is associated with allergic rhinitis (AR). This article aims to demystify the role of FOXD3-AS1 in AR. We compared FOXD3-AS1 expression in nasal mucosas between AR patients and healthy control. Next, nasal epithelial cells (NECs) were incubated with lipopolysaccharide or recombinant IL-25, and then the supernatant of the NECs was incubated with CD4+ T cells. Th2 cell proportions were assessed by flow cytometry. The levels of gene and cytokines were detected by real-time quantitative PCR or enzyme linked immunosorbent assay. FOXD3-AS1 was downregulated in nasal mucosas of AR patients, whereas Th2 cell proportions and the levels of IL-25, IL-4, and IL-13 were enhanced in peripheral blood of AR patients. FOXD3-AS1 overexpression inhibited the expression and secretion of IL-25 in NECs. The levels of IL-4 and IL-13 and Th2 cell proportions in CD4+ T cells were enhanced by recombinant IL-25, which was effectively abolished by the supernatant of FOXD3-AS1-overexpressed NECs treatment. Our study demonstrates that FOXD3-AS1 is downregulated in nasal mucosas of AR patients, and FOXD3-AS1 represses the expression and secretion IL-25 in NECs, thereby inhibiting Th2 type immunoreaction in AR. Thus, our data provide a novel target gene for AR treatment.

Keywords: Allergic rhinitis; FOXD3-AS1; IL-25; Long non-coding RNA; Th2 type immunoreaction.

MeSH terms

  • Epithelial Cells / immunology*
  • Epithelial Cells / pathology
  • Female
  • Gene Expression Regulation / immunology*
  • Humans
  • Interleukin-17 / immunology*
  • Male
  • Nasal Mucosa / immunology*
  • Nasal Mucosa / pathology
  • RNA, Long Noncoding / immunology*
  • Rhinitis, Allergic / immunology*
  • Rhinitis, Allergic / pathology
  • Th2 Cells / immunology*
  • Th2 Cells / pathology

Substances

  • IL25 protein, human
  • Interleukin-17
  • RNA, Long Noncoding