| First Author | Yao C | Year | 2021 |
| Journal | Nat Immunol | Volume | 22 |
| Issue | 3 | Pages | 370-380 |
| PubMed ID | 33574619 | Mgi Jnum | J:305256 |
| Mgi Id | MGI:6705162 | Doi | 10.1038/s41590-021-00868-7 |
| Citation | Yao C, et al. (2021) BACH2 enforces the transcriptional and epigenetic programs of stem-like CD8(+) T cells. Nat Immunol 22(3):370-380 |
| abstractText | During chronic infection and cancer, a self-renewing CD8(+) T cell subset maintains long-term immunity and is critical to the effectiveness of immunotherapy. These stem-like CD8(+) T cells diverge from other CD8(+) subsets early after chronic viral infection. However, pathways guarding stem-like CD8(+) T cells against terminal exhaustion remain unclear. Here, we show that the gene encoding transcriptional repressor BACH2 is transcriptionally and epigenetically active in stem-like CD8(+) T cells but not terminally exhausted cells early after infection. BACH2 overexpression enforced stem-like cell fate, whereas BACH2 deficiency impaired stem-like CD8(+) T cell differentiation. Single-cell transcriptomic and epigenomic approaches revealed that BACH2 established the transcriptional and epigenetic programs of stem-like CD8(+) T cells. In addition, BACH2 suppressed the molecular program driving terminal exhaustion through transcriptional repression and epigenetic silencing. Thus, our study reveals a new pathway that enforces commitment to stem-like CD8(+) lineage and prevents an alternative terminally exhausted cell fate. |
