| First Author | Chen L | Year | 2024 |
| Journal | Adv Sci (Weinh) | Volume | 11 |
| Issue | 28 | Pages | e2401654 |
| PubMed ID | 38650111 | Mgi Jnum | J:360490 |
| Mgi Id | MGI:7797635 | Doi | 10.1002/advs.202401654 |
| Citation | Chen L, et al. (2024) T-bet Regulates Ion Channels and Transporters and Induces Apoptosis in Intestinal Epithelial Cells. Adv Sci (Weinh) 11(28):e2401654 |
| abstractText | 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(+) T cells or myeloid lineages. Instead, inducible T-bet overexpression in the intestinal epithelial cells is the critical determinant of the observed lethal phenotype. Mechanistically, T-bet overexpression modulates ion channel and transporter profiles in gut epithelial cells, triggering profound fluid secretion and subsequent lethal dehydration. Furthermore, ectopic T-bet expression enhances gut epithelial cell apoptosis and markedly suppresses colon cancer development in xenograft models. Collectively, the findings unveil a previously unrecognized role of T-bet in intestinal epithelial cells for inducing apoptosis, diarrhea, and local inflammation, thus implicating its potential as a therapeutic target for the treatment of cancer and inflammatory diseases. |
