| First Author | Dominguez CX | Year | 2015 |
| Journal | J Exp Med | Volume | 212 |
| Issue | 12 | Pages | 2041-56 |
| PubMed ID | 26503446 | Mgi Jnum | J:228509 |
| Mgi Id | MGI:5707534 | Doi | 10.1084/jem.20150186 |
| Citation | Dominguez CX, et al. (2015) The transcription factors ZEB2 and T-bet cooperate to program cytotoxic T cell terminal differentiation in response to LCMV viral infection. J Exp Med 212(12):2041-2056 |
| abstractText | The transcription factor T-bet is critical for cytotoxic T lymphocyte (CTL) differentiation, but it is unclear how it operates in a graded manner in the formation of both terminal effector and memory precursor cells during viral infection. We find that, at high concentrations, T-bet induced expression of Zeb2 mRNA, which then triggered CTLs to adopt terminally differentiated states. ZEB2 and T-bet cooperate to switch on a terminal CTL differentiation program, while simultaneously repressing genes necessary for central memory CTL development. Chromatin immunoprecipitation sequencing showed that a large proportion of these genes were bound by T-bet, and this binding was altered by ZEB2 deficiency. Furthermore, T-bet overexpression could not fully bypass ZEB2 function. Thus, the coordinated actions of T-bet and ZEB2 outline a novel genetic pathway that forces commitment of CTLs to terminal differentiation, thereby restricting their memory cell potential. |
