| First Author | Jiao A | Year | 2022 |
| Journal | Sci Adv | Volume | 8 |
| Issue | 6 | Pages | eabk2691 |
| PubMed ID | 35138904 | Mgi Jnum | J:326041 |
| Mgi Id | MGI:6885071 | Doi | 10.1126/sciadv.abk2691 |
| Citation | Jiao A, et al. (2022) DExD/H-box helicase 9 intrinsically controls CD8(+) T cell-mediated antiviral response through noncanonical mechanisms. Sci Adv 8(6):eabk2691 |
| abstractText | 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 CD3epsilon-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. |
