Yao, Chen and Lou, Guohua and Sun, Hong-Wei and Zhu, Ziang and Sun, Yi and Chen, Zeyu and Chauss, Daniel and Moseman, E. Ashley and Cheng, Jun and D'Antonio, Marc A. and Shi, Wangke and Shi, Junwei and Kometani, Kohei and Kurosaki, Tomohiro and Wherry, E. John and Afzali, Behdad and Gattinoni, Luca and Zhu, Yuwen and McGavern, Dorian B. and O'Shea, John J. and Schwartzberg, Pamela L. and Wu, Tuoqi (2021) BACH2 enforces the transcriptional and epigenetic programs of stem-like CD8(+) T cells. NATURE IMMUNOLOGY, 22 (3). 370-+. ISSN 1529-2908, 1529-2916
Full text not available from this repository. (Request a copy)Abstract
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. Tuoqi Wu and colleagues show that the transcriptional repressor BACH2 is required early after chronic viral infection to enforce a stem-like fate in activated CD8(+) T cells. BACH2 acts to suppress genes that lead to the exhausted cell state.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Zentren des Universitätsklinikums Regensburg > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 21 Sep 2022 13:48 |
| Last Modified: | 21 Sep 2022 13:48 |
| URI: | https://pred.uni-regensburg.de/id/eprint/47872 |
Actions (login required)
 |
View Item |
