Gliadin, through the Activation of Innate Immunity, Triggers lncRNA NEAT1 Expression in Celiac Disease Duodenal Mucosa

Int J Mol Sci. 2021 Jan 28;22(3):1289. doi: 10.3390/ijms22031289.


Celiac disease (CD) is an autoimmune enteropathy arising in genetically predisposed subjects exposed to gluten, which activates both innate and adaptive immunity. Although the pathogenesis is common to all patients, the clinical spectrum is quite variable, and differences could be explained by gene expression variations. Among the factors able to affect gene expression, there are lncRNAs. We evaluated the expression profile of 87 lncRNAs in CD vs. healthy control (HC) intestinal biopsies by RT-qPCR array. Nuclear enriched abundant transcript 1 (NEAT1) and taurine upregulated gene 1 (TUG1) were detected as downregulated in CD patients at diagnosis, but their expression increased in biopsies of patients on a gluten-free diet (GFD) exposed to gluten. The increase in NEAT1 expression after gluten exposure was mediated by IL-15 and STAT3 activation and binding to the NEAT1 promoter, as demonstrated by gel shift assay. NEAT1 is localized in the nucleus and can regulate gene expression by sequestering transcription factors, and it has been implicated in immune regulation and control of cell proliferation. The demonstration of its regulation by gluten thus also supports the role of lncRNAs in CD and prompts further research on these RNAs as gene expression regulators.

Keywords: NEAT1; TUG1; celiac disease; innate immunity; long non-coding RNAs.

MeSH terms

  • Adult
  • Case-Control Studies
  • Celiac Disease / genetics*
  • Celiac Disease / immunology
  • Cell Proliferation
  • Cells, Cultured
  • Child
  • Down-Regulation* / drug effects
  • Duodenum / chemistry*
  • Duodenum / immunology
  • Female
  • Gene Expression Regulation
  • Gliadin / adverse effects*
  • Humans
  • Immunity, Innate
  • Interleukin-15 / genetics
  • Intestinal Mucosa / chemistry
  • Intestinal Mucosa / immunology
  • Male
  • RNA, Long Noncoding / genetics*
  • STAT3 Transcription Factor / genetics


  • IL15 protein, human
  • Interleukin-15
  • NEAT1 long non-coding RNA, human
  • RNA, Long Noncoding
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • TUG1 long noncoding RNA, human
  • Gliadin