The Loss of YTHDC1 in Gut Macrophages Exacerbates Inflammatory Bowel Disease.

ABSTRACT: The nuclear N⁶ -methyladenosine (m⁶ A) reader YT521-B homology-domain-containing protein 1 (YTHDC1) is required to maintain embryonic stem cell identity. However, little is known about its biological functions in intestinal-resident macrophages and inflammatory bowel disease (IBD). Herein, it is demonstrated that macrophage-specific depletion or insufficiency of YTHDC1 accelerates IBD development in animal models. On the molecular basis, YTHDC1 reduction in IBD-derived macrophages is attributed to Zinc finger protein 36 (ZFP36)-induced mRNA degradation. Importantly, transcriptome profiling and mechanistic assays unveil that YTHDC1 in macrophages regulates Ras homolog family member H (RHOH) to suppress inflammatory responses and fine-tunes NME nucleoside diphosphate ki

SUBMITTER: Ge X 

PROVIDER: S-EPMC10190588 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature