| Autor: |
Anjun Jiao, Chenming Sun, Xin Wang, Lei Lei, Haiyan Liu, Wenhui Li, Xiaofeng Yang, Huiqiang Zheng, Renyi Ding, Kun Zhu, Yanhong Su, Cangang Zhang, Lianjun Zhang, Baojun Zhang |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Science Advances. 8 |
| ISSN: |
2375-2548 |
| DOI: |
10.1126/sciadv.abk2691 |
| Popis: |
Upon virus infection, CD8 + T cell accumulation is tightly controlled by simultaneous proliferation and apoptosis. However, it remains unclear how TCR signal coordinates these events to achieve expansion and effector cell differentiation. We found that T cell–specific deletion of nuclear helicase Dhx9 led to impaired CD8 + T cell survival, effector differentiation, and viral clearance. Mechanistically, Dhx9 acts as the key regulator to ensure LCK- and CD3ε-mediated ZAP70 phosphorylation and ERK activation to protect CD8 + T cells from apoptosis before proliferative burst. Dhx9 directly regulates Id2 transcription to control effector CD8 + T cell differentiation. The DSRM and OB_Fold domains are required for LCK binding and Id2 transcription, respectively. Dhx9 expression is predominantly increased in effector CD8 + T cells of COVID-19 patients. Therefore, we revealed a previously unknown regulatory mechanism that Dhx9 protects activated CD8 + T cells from apoptosis and ensures effector differentiation to promote antiviral immunity independent of nuclear sensor function. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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