Reduction of m6A RNA methylation ameliorates antiviral response in celiac disease

Reduction of m6A RNA methylation ameliorates antiviral response in celiac disease | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Reduction of m6A RNA methylation ameliorates antiviral response in celiac disease Ainara Castellanos-Rubio, Maialen Sebastian-delaCruz, Ane Olazagoitia-Garmendia, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6421004/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 10 Jan, 2026 Read the published version in Genes & Immunity → Version 1 posted 15 You are reading this latest preprint version Abstract m6A RNA modifications and reovirus infections have recently been involved in the development of celiac disease. Moreover, viral infections are linked to alterations in the RNA modification machinery of the host, but the link between these two events has not been studied in the context of autoimmunity driven tissue damage. Here we used an in vitro model of viral mimic combined with gliadin peptides, resembling celiac disease, together with sera and intestinal biopsies of controls and patients to describe the relationship between m6A methylation and viral infections in inducing autoimmunity related inflammation. We found elevated anti-reovirus reactivity in patients, together with higher antiviral gene expression and m6A induction. Additionally, we described a synergistic increase of IRF7 expression upon simultaneous exposure to the viral mimic and gliadin peptides is mediated by the presence of m6A motifs within its CDS and interaction with YTHDC2 reader protein. Furthermore, our findings revealed that reduction of m6A by METTL3 silencing or simvastatin treatment reduce IRF7 methylation and downstream inflammatory gene expression in vitro and ex vivo, opening new avenues for therapeutic interventions in autoimmune disorders. Biological sciences/Immunology/Bone marrow transplantation Biological sciences/Immunology/Mucosal immunology Full Text Additional Declarations There is NO conflict of interest to disclose. Authors declare NO conflict of interest Supplementary Files SUPPLEMENTARYFIGURESANDLEGENDS.pdf Supplementary Figures Cite Share Download PDF Status: Published Journal Publication published 10 Jan, 2026 Read the published version in Genes & Immunity → Version 1 posted Editorial decision: revise 27 Jun, 2025 Review # 4 received at journal 10 Jun, 2025 Review # 5 received at journal 02 Jun, 2025 Review # 3 received at journal 29 May, 2025 Reviewer # 5 agreed at journal 24 May, 2025 Review # 2 received at journal 18 May, 2025 Reviewer # 4 agreed at journal 12 May, 2025 Reviewer # 3 agreed at journal 09 May, 2025 Reviewer # 2 agreed at journal 09 May, 2025 Reviewer # 1 agreed at journal 09 May, 2025 Reviewers invited by journal 08 May, 2025 Submission checks completed at journal 24 Apr, 2025 First submitted to journal 21 Apr, 2025 Unknown event 17 Apr, 2025 Editor assigned by journal 10 Apr, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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