Bibliographic Details
| Title: |
The pseudokinase Trib1 regulates the transition of exhausted T cells to a KLR+ CD8+ effector state, and its deletion improves checkpoint blockade |
| Authors: |
Susan E. McClory, Oishi Bardhan, Kelly S. Rome, Josephine R. Giles, Amy E. Baxter, Lanwei Xu, Phyllis A. Gimotty, Robert B. Faryabi, E. John Wherry, Warren S. Pear, Martha S. Jordan |
| Source: |
Cell Reports, Vol 42, Iss 8, Pp 112905- (2023) |
| Publisher Information: |
Elsevier, 2023. |
| Publication Year: |
2023 |
| Collection: |
LCC:Biology (General) |
| Subject Terms: |
CP: Immunology, Biology (General), QH301-705.5 |
| More Details: |
Summary: CD8+ T cell exhaustion (TEX) impairs the ability of T cells to clear chronic infection or cancer. While TEX are hypofunctional, some TEX retain effector gene signatures, a feature associated with killer lectin-like receptor (KLR) expression. Although KLR+ TEX (TKLR) 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 TEX toward CX3CR1+ intermediates with robust enrichment of TKLR via clonal T cell expansion. Adoptive transfer studies demonstrate this shift toward CD8+ TKLR 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+ TEX whose targeting enhances the TKLR effector state and improves checkpoint inhibitor therapy. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2211-1247 |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S2211124723009166; https://doaj.org/toc/2211-1247 |
| DOI: |
10.1016/j.celrep.2023.112905 |
| Access URL: |
https://doaj.org/article/649d5307b00c4acca7e424a01f75bf3e |
| Accession Number: |
edsdoj.649d5307b00c4acca7e424a01f75bf3e |
| Database: |
Directory of Open Access Journals |
