T-bet Regulates Ion Channels and Transporters and Induces Apoptosis in Intestinal Epithelial Cells

Authors

Lang Chen
Hongwei Yi
Qingtian Li
Tianhao Duan
Xin Liu
Linfeng Li
Helen Y Wang
Changsheng Xing
Rong-Fu Wang

Publication Date

7-1-2024

Journal

Advanced Science

DOI

10.1002/advs.202401654

PMID

38650111

PMCID

PMC11267362

PubMedCentral® Posted Date

4-22-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Animals, Mice, Apoptosis, T-Box Domain Proteins, Mice, Transgenic, Ion Channels, Epithelial Cells, Intestinal Mucosa, Humans, Disease Models, Animal, cancer therapy, cell apoptosis, intestinal epithelial cells, ion channels and transporters, T‐bet

Abstract

T-bet, encoded by TBX21, is extensively expressed across various immune cell types, and orchestrates critical functions in their development, survival, and physiological activities. However, the role of T-bet in non-immune compartments, notably the epithelial cells, remains obscure. Herein, a Tet-O-T-bet transgenic mouse strain is generated for doxycycline-inducible T-bet expression in adult animals. Unexpectedly, ubiquitous T-bet overexpression causes acute diarrhea, intestinal damage, and rapid mortality. Cell-type-specific analyses reveal that T-bet-driven pathology is not attributable to its overexpression in CD4