Equipe: Xavier MarietteÂ
Financements: ANR JC METRESS, HEATHI MERCATO, HEADS TECHNICS PARIS-SG et FRM PERMESSÂ
Salivary gland epithelial cells (SGECs) play a critical role in the development of Sjögren’s disease (SjD), functioning as both targets of autoimmune attack and contributors to inflammation. While recent research has emphasized the importance of post-transcriptional mRNA modifications, particularly N6-methyladenosine (m6A) RNA methylation, in gene regulation, the role of these modifications in SGEC function and their involvement in autoimmune diseases like SjD remained unexamined. This study reveals that m6A methylation serves as a negative feedback mechanism in SGECs, controlling excessive inflammation through Poly(I:C) and interferon signaling. A deficiency in METTL3, a key component of the m6A pathway, leads to abnormal double-stranded RNA production, contributing to SjD pathogenesis. SjD patients also exhibit insufficient METTL3 upregulation during inflammation, indicating a compromised ability to regulate the inflammatory response, particularly in those with high disease activity and elevated interferon signatures. These findings suggest that METTL3 could serve as a biomarker for disease prognosis and stratification, and understanding the impact of m6A modifications on SGECs may lead to new targeted therapies that preserve SGEC function and improve outcomes for SjD patients.
