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.
【초록키워드】 Apoptosis, T cells, Transcription, CD8, viral clearance, Helicase, Regulatory, T cell, survival, Phosphorylation, virus infection, antiviral immunity, TCR, expression, mechanism, COVID-19 patients, binding, regulate, proliferation, independent of, Activation, domain, effector, nuclear, ERK, event, independent, DHX9, ZAP70, PROTECT, required, activated, promote, Coordinate, proliferative, effector cell, LCK, 【제목키워드】 CD8, Helicase, Control, mechanism, antiviral response, intrinsically,