DExD/H-box helicase 9 intrinsically controls CD8⁺ T cell-mediated antiviral response through noncanonical mechanisms.

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 transcrip

SUBMITTER: Jiao A 

PROVIDER: S-EPMC8827654 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature