| First Author | Murphy MK | Year | 2025 |
| Journal | Immunity | Volume | 58 |
| Issue | 10 | Pages | 2472-2488.e9 |
| PubMed ID | 41043414 | Mgi Jnum | J:373572 |
| Mgi Id | MGI:8253972 | Doi | 10.1016/j.immuni.2025.09.008 |
| Citation | Murphy MK, et al. (2025) The transcriptional repressor BLIMP1 enforces TCF-1-dependent and -independent restriction of the memory fate of CD8(+) T cells. Immunity 58(10):2472-2488.e9 |
| abstractText | During differentiation of CD8(+) T cells, the transcription factors TCF-1 and Blimp1 control progenitor and terminally differentiated states, respectively. Here, we examined the hierarchy and functional consequences of cross-regulation between these factors. We identified two Blimp1-bound cis-regulatory elements, Tcf7(+22kb) and Tcf7(+17kb), that enforced Tcf7 silencing in a context-specific manner during both acute and chronic responses. Deletion of these elements decoupled Tcf7 repression from effector differentiation but did not rewire effector T cells to a memory state or prevent the acquisition of phenotypic hallmarks of exhaustion. However, combined ablation of Prdm1 and Tcf7 preserved a memory surface phenotype despite defects in secondary expansion. Thus, the anti-proliferative and pro-differentiative effects of Blimp1 in effector or exhausted CD8(+) T cells represent mechanistically distinct modules, wherein repression of Tcf7 limits proliferative capacity but not memory or progenitor specification. |
