Zbtb44-mediated transcriptional repression critically regulates colonic inflammation

ABSTRACT: The regulatory mechanisms that maintain colonic immune homeostasis remain incompletely understood. Here, we show that genetic deletion of Zbtb44, a previously uncharacterized member of the ZBTB transcription factor family, leads to spontaneous colitis and rectal prolapse. Zbtb44−/− T cells expressed increased IFN-g, a pro-inflammatory cytokine strongly associated with human inflammatory bowel disease (IBD). Mechanistically, Zbtb44 undergoes SUMOylation, which facilitates its interaction with a conserved SUMO-interacting motif (SIM) in T-bet, enabling binding to the IFN-g promoter and enhancer to restrain chronic IFN-g production. Together, these findings demonstrate that Zbtb44 is a key regulator of colonic inflammation, a role that could be exploited therapeutically.

ORGANISM(S): Mus musculus

PROVIDER: GSE294267 | GEO | 2026/09/01

REPOSITORIES: GEO