NAT10-mediated acetylation of NIK mRNA in B cells promotes IgA production

The regulation of IgA expression is crucial for maintaining mucosal immune homeostasis, providing a vital defense mechanism against pathogens at mucosal surfaces. However, the intricate mechanisms governing IgA class-switch recombination and its dysregulation in diseases such as inflammatory bowel disease remain a significant challenge in the field. Our study delves into the significance of IgA regulation in mucosal immunity, focusing on the N⁴-acetylcytidine (ac⁴C) in NIK mRNA by NAT10 in B cells. We discovered that NAT10-mediated ac⁴C stabilizes NIK mRNA, thereby promoting IgA production, which is pivotal for immune defense. Our findings in a B-cell conditional NAT10 knockout mouse model highlight a reduction in IgA expression and a dampened noncanonical NF-κB pathway, suggesting NAT10 as a potential therapeutic target for IgA-related disorders. This research provides novel insights into the post-transcriptional regulation of IgA and underscores the role of NAT10 in modulating mucosal immunity.