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m6A RNA methylation modulates antiviral response in celiac disease

Maialen Sebastian-delaCruz1,2, Ane Olazagoitia-Garmendia1,2, Izei Pascual-Gonzalez1,2

  • 1University of the Basque Country (UPV-EHU), Leioa, Spain.

Genes and Immunity
|January 9, 2026
PubMed

Insights

N6-methyladenosine (m6A) RNA modifications and reovirus infections are linked to celiac disease. This study shows m6A methylation regulates antiviral responses and inflammation, offering a potential therapeutic target for autoimmune disorders.

Area of Science:

  • Immunology
  • Molecular Biology
  • Gastroenterology

Background:

  • Celiac disease involves autoimmune tissue damage, with N6-methyladenosine (m6A) RNA modifications and reovirus infections emerging as potential contributors.
  • The interplay between viral infections, RNA modification machinery, and autoimmune pathogenesis is not well understood.

Purpose of the Study:

  • To investigate the link between m6A methylation, viral infections, and autoimmune inflammation in celiac disease.
  • To explore the role of m6A in regulating antiviral gene expression and its potential as a therapeutic target.

Main Methods:

  • Utilized an in vitro model with a viral mimic and gliadin peptides to simulate celiac disease conditions.
  • Analyzed serum and intestinal biopsies from celiac disease patients and controls.
  • Investigated the expression of IRF7 and its regulation by m6A methylation and YTHDC2.

Main Results:

  • Patients showed elevated anti-reovirus reactivity, increased antiviral gene expression, and enhanced m6A levels.
  • Combined exposure to viral mimic and gliadin synergistically induced IRF7 expression via m6A methylation and YTHDC2 interaction.
  • METTL3 silencing or simvastatin treatment reduced m6A, IRF7 methylation, and pro-inflammatory gene expression.

Conclusions:

  • m6A RNA methylation acts as a key modulator of antiviral responses in the context of celiac disease.
  • Targeting m6A methylation pathways presents a potential therapeutic strategy for autoimmune disorders like celiac disease.

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