Gliadin, through the activation of innate immunity, triggers lncrna neat1 expression in celiac disease duodenal mucosa

Elisa Gnodi, Clara Mancuso, Luca Elli, Elisa Ballarini, Raffaella Meneveri, Jean François Beaulieu, Donatella Barisani

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number1289
Number of pages15
JournalInternational Journal of Molecular Sciences
Volume22
Issue number3
DOIs
Publication statusPublished - Feb 1 2021

Keywords

  • Celiac disease
  • Innate immunity
  • Long non-coding RNAs
  • NEAT1
  • TUG1

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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