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

ABSTRACT: CD8⁺ T cell exhaustion (T_EX) impairs the ability of T cells to clear chronic infection or cancer. While T_EX are hypofunctional, some T_EX retain effector gene signatures, a feature associated with killer lectin-like receptor (KLR) expression. Although KLR⁺ T_EX (T_KLR) may improve control of chronic antigen, the signaling molecules regulating this population are poorly understood. Using single-cell RNA sequencing (scRNA-seq), flow cytometry, RNA velocity, and single-cell T cell receptor sequencing (scTCR-seq), we demonstrate that deleting the pseudokinase Trib1 shifts T_EX toward CX3CR1⁺ intermediates with robust enrichment of T_KLR via clonal T cell expansion. Adoptive transfer studies

SUBMITTER: McClory SE 

PROVIDER: S-EPMC10540077 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature