biostudies-literatureUnknownMcClory SENIAID NIH HHSNCI NIH HHST 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 inbioRxiv : the preprint server for biology2023.02.16.528833https://www.ebi.ac.uk/biostudies/studies/S-EPMC9948998biostudies-literatureThe pseudokinase Trib1 regulates the transition of exhausted T cells to a KLR ⁺ CD8 ⁺ effector state and its deletion improves checkpoint blockade.PMC9948998R01 AI155577P30 CA016520T32 CA009140P01 AI108545P01 CA210944U19 AI082630T32 CA009615R01 AI115712R01 AI047833K12 CA076931U19 AI117950Xu LGiles JRPear WSRome KSBaxter AEWherry EJBardhan OGimotty PAFaryabi RBJordan MSMcClory SEfalseThe pseudokinase Trib1 regulates the transition of exhausted T cells to a KLR ⁺ CD8 ⁺ effector state and its deletion improves checkpoint blockade.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 in2023-01-01T00:00:00Z2023 Feb2025-04-04T13:08:03.258Z2025-04-04T13:08:03.258ZS-EPMC99489983682493110.1101/2023.02.16.528833