Projects per year
Abstract
Integration of a large network of kinase signalling pathways co-ordinates changes in the transcription, translation and metabolic events required for T cell activation and differentiation. The present study explores the role of the Serine/Threonine kinases PIM1 and PIM2 in controlling murine CD8 T lymphocyte antigen receptor-mediated activation and differentiation in response to the cytokines Interleukin 2 (IL-2) or IL-15. We show that PIM kinases are dispensable for the differentiation programs controlled by the antigen-receptor and IL-15. There is however a selective role for the PIM kinases in the context of IL-2 regulation of CD8 T cell fate. One key insight was that the PIM kinases controlled the migratory capabilities of effector CD8 T cells, with Pim1/Pim2-deficient CD8 T cells unable to fully switch off the naïve T cell chemokine and adhesion receptor program during effector differentiation. PIM kinases were also needed for IL-2 to sustain high expression of the glucose transporters SLC2A1 and SLC2A3 and to maintain activity of the nutrient sensing kinase mTORc1. Strikingly, PIM kinases did not have a dominant impact on IL-2-driven transcriptional programs but rather selectively modulated protein synthesis to shape cytotoxic T cell proteomes. This study reveals a selective role of PIM kinases in IL-2 control of CD8 T cells and highlights how regulated changes in protein synthesis can impact T cell phenotypes.
Original language | English |
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Pages (from-to) | 1-33 |
Number of pages | 33 |
Journal | eLife |
Early online date | 16 Jul 2024 |
DOIs | |
Publication status | Published - 24 Jul 2024 |
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Dive into the research topics of 'PIM kinase control of CD8 T cell protein synthesis and cell trafficking'. Together they form a unique fingerprint.Projects
- 3 Finished
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Unravelling How Protein Signalling Networks Integrate to Control T Cell Fate (PIM PROTEOMICS)
Cantrell, D. (Investigator) & Marchingo, J. (Investigator)
COMMISSION OF THE EUROPEAN COMMUNITIES
14/07/17 → 13/07/19
Project: Research
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Fluorescence Activated Cell Sorting for Cell Biology and Immunology (Equipment Grant)
Cantrell, D. (Investigator)
1/09/16 → 1/12/19
Project: Research
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Serine Kinase Pathways that Determine T Lymphocyte Activation and Cell Fate Choices (Principal Research Fellowship renewal)
Cantrell, D. (Investigator)
1/10/12 → 1/10/24
Project: Research