| First Author | Guan T | Year | 2018 |
| Journal | J Exp Med | Volume | 215 |
| Issue | 4 | Pages | 1153-1168 |
| PubMed ID | 29449309 | Mgi Jnum | J:261592 |
| Mgi Id | MGI:6155775 | Doi | 10.1084/jem.20171352 |
| Citation | Guan T, et al. (2018) ZEB1, ZEB2, and the miR-200 family form a counterregulatory network to regulate CD8(+) T cell fates. J Exp Med 215(4):1153-1168 |
| abstractText | Long-term immunity depends partly on the establishment of memory CD8(+) T cells. We identified a counterregulatory network between the homologous transcription factors ZEB1 and ZEB2 and the miR-200 microRNA family, which modulates effector CD8(+) T cell fates. Unexpectedly, Zeb1 and Zeb2 had reciprocal expression patterns and were functionally uncoupled in CD8(+) T cells. ZEB2 promoted terminal differentiation, whereas ZEB1 was critical for memory T cell survival and function. Interestingly, the transforming growth factor beta (TGF-beta) and miR-200 family members, which counterregulate the coordinated expression of Zeb1 and Zeb2 during the epithelial-to-mesenchymal transition, inversely regulated Zeb1 and Zeb2 expression in CD8(+) T cells. TGF-beta induced and sustained Zeb1 expression in maturing memory CD8(+) T cells. Meanwhile, both TGF-beta and miR-200 family members selectively inhibited Zeb2. Additionally, the miR-200 family was necessary for optimal memory CD8(+) T cell formation. These data outline a previously unknown genetic pathway in CD8(+) T cells that controls effector and memory cell fate decisions. |
