Epithelium intrinsic zinc sensor controls immune homeostasis with gut microbes via regulation of Tuft cell lineage.

ABSTRACT: Zinc is an essential micronutrient crucial for cell proliferation, differentiation, and apoptosis, yet its precise role in the constantly renewing intestinal epithelium remains unclear. We generated mice lacking the Zn-dependent transcription factor Metal-responsive Transcription Factor 1(MTF1^ΔIEC) in intestinal epithelial cells. MTF1^ΔIEC mice exhibited altered metal homeostasis and acute susceptibility to Zn supplementation. Transcriptional and cellular analyses revealed increased inflammatory immune responses to microbes in MTF1^ΔIEC mice. Mechanistically MTF1 deletion resulted in the loss of Tuft cell lineages compromising barrier function against commensal microbes and pathogens. Ex vivo experiments demonstrated that at a cellular level, Zn treatment ske

SUBMITTER: Yunker R 

PROVIDER: S-EPMC12132379 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature