DExD/H-box helicase 9 intrinsically controls CD8+ T cell-mediated antiviral response through noncanonical mechanisms.
Sci Adv
; 8(6): eabk2691, 2022 02 11.
Article
in English
| MEDLINE | ID: covidwho-1685473
ABSTRACT
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Arenaviridae Infections
/
CD8-Positive T-Lymphocytes
/
DEAD-box RNA Helicases
/
COVID-19
/
Immunity, Innate
/
Neoplasm Proteins
Type of study:
Experimental Studies
/
Prognostic study
Limits:
Animals
/
Humans
Language:
English
Journal:
Sci Adv
Year:
2022
Document Type:
Article
Affiliation country:
Sciadv.abk2691
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