The pseudokinase Trib1 regulates the transition of exhausted T cells to a KLR ⁺ CD8 ⁺ effector state and its deletion improves checkpoint blockade.

ABSTRACT: T cell exhaustion (T _EX ) impairs the ability of T cells to clear chronic infection or cancer. While exhausted T cells are hypofunctional, some exhausted T cells retain effector gene signatures, a feature that is associated with expression of KLRs (killer lectin-like receptors). Although KLR ⁺ T cells may improve control of chronic antigen, the signaling molecules regulating this population are poorly understood. Using scRNA-seq, flow cytometry, RNA velocity, and scTCR-seq, we demonstrate that deleting the pseudokinase Trib1 shifts T _EX towards CX3CR1 ⁺ intermediates (T _INT ) with robust enrichment of KLR ⁺ CD8 ⁺ T cells (T _KLR ) via clonal T cell expansion. These changes are associated with globally in

SUBMITTER: McClory SE 

PROVIDER: S-EPMC9948998 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature