{"doi":"10.1016/j.celrep.2023.112905","title":"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 demonstrate this shift toward CD8 + T KLR in Trib1-deficient cells is CD8 intrinsic, while CD4-depletion studies demonstrate CD4 + T cells are required for improved viral control in Trib1 conditional knockout mice. Further, Trib1 loss augments anti-programmed death-ligand 1 (PD-L1) blockade to improve viral clearance. These data identify Trib1 as an important regulator of CD8 + T EX whose targeting enhances the T KLR effector state and improves checkpoint inhibitor therapy.","journal":"Cell Reports","year":2023,"id":357926,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9451,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":833547,"name":"Oishi Bardhan","orcid":null,"position":1,"is_corresponding":false},{"id":485222,"name":"Kelly Rome","orcid":"0000-0002-0703-1788","position":2,"is_corresponding":false},{"id":105447,"name":"Josephine R. Giles","orcid":"0000-0002-3713-338X","position":3,"is_corresponding":false},{"id":105448,"name":"Amy E. Baxter","orcid":"0000-0002-1555-0713","position":4,"is_corresponding":false},{"id":485226,"name":"Lanwei Xu","orcid":"0000-0003-1932-5799","position":5,"is_corresponding":false},{"id":325359,"name":"Phyllis A. Gimotty","orcid":"0000-0002-3850-9799","position":6,"is_corresponding":false},{"id":324342,"name":"Robert B. Faryabi","orcid":"0000-0002-7931-2175","position":7,"is_corresponding":false},{"id":36451,"name":"E. John Wherry","orcid":"0000-0003-0477-1956","position":8,"is_corresponding":false},{"id":853,"name":"Warren S. Pear","orcid":"0000-0002-2624-0526","position":9,"is_corresponding":false},{"id":296325,"name":"Martha S. Jordan","orcid":"0000-0003-2359-3227","position":10,"is_corresponding":false},{"id":485225,"name":"Susan McClory","orcid":"0000-0002-4607-5230","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-19T01:13:39.186262Z","pmid":"37527035","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}