PIM kinase control of CD8 T cell protein synthesis and cell trafficking
Integration of kinase signalling networks co-ordinates the transcriptional, translational, and metabolic changes required for T cell activation and differentiation. This study explores the role of the Serine/Threonine kinases PIM1 and PIM2 in controlling mouse CD8 T lymphocyte antigen receptor-media...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2025-05-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/98622 |
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| _version_ | 1849312824125292544 |
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| author | Julia M Marchingo Laura Spinelli Shalini Pathak Doreen A Cantrell |
| author_facet | Julia M Marchingo Laura Spinelli Shalini Pathak Doreen A Cantrell |
| author_sort | Julia M Marchingo |
| collection | DOAJ |
| description | Integration of kinase signalling networks co-ordinates the transcriptional, translational, and metabolic changes required for T cell activation and differentiation. This study explores the role of the Serine/Threonine kinases PIM1 and PIM2 in controlling mouse CD8 T lymphocyte antigen receptor-mediated activation and differentiation in response to the cytokines Interleukin-2 (IL-2) or IL-15. We show that the PIM kinases are dispensable for antigen-receptor and IL-15 controlled differentiation programs, but that they play a selective role in IL-2 regulated CD8 T cell fate. One key insight was that PIM kinases controlled the migratory capabilities of effector CD8 T cells, with Pim1/Pim2-deficient CD8 T cells unable to fully switch off the naive 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. |
| format | Article |
| id | doaj-art-5312bc3dc9be456f91063ca26347a3a9 |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-5312bc3dc9be456f91063ca26347a3a92025-08-20T03:52:57ZengeLife Sciences Publications LtdeLife2050-084X2025-05-011310.7554/eLife.98622PIM kinase control of CD8 T cell protein synthesis and cell traffickingJulia M Marchingo0https://orcid.org/0000-0001-8823-9718Laura Spinelli1https://orcid.org/0000-0002-5801-6297Shalini Pathak2Doreen A Cantrell3https://orcid.org/0000-0001-7525-3350Cell Signalling and Immunology Division, School of Life Sciences, University of Dundee, Dundee, United KingdomCell Signalling and Immunology Division, School of Life Sciences, University of Dundee, Dundee, United Kingdom; Molecular Cell and Developmental Biology Division, School of Life Sciences, University of Dundee, Dundee, United KingdomCell Signalling and Immunology Division, School of Life Sciences, University of Dundee, Dundee, United KingdomCell Signalling and Immunology Division, School of Life Sciences, University of Dundee, Dundee, United KingdomIntegration of kinase signalling networks co-ordinates the transcriptional, translational, and metabolic changes required for T cell activation and differentiation. This study explores the role of the Serine/Threonine kinases PIM1 and PIM2 in controlling mouse CD8 T lymphocyte antigen receptor-mediated activation and differentiation in response to the cytokines Interleukin-2 (IL-2) or IL-15. We show that the PIM kinases are dispensable for antigen-receptor and IL-15 controlled differentiation programs, but that they play a selective role in IL-2 regulated CD8 T cell fate. One key insight was that PIM kinases controlled the migratory capabilities of effector CD8 T cells, with Pim1/Pim2-deficient CD8 T cells unable to fully switch off the naive 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.https://elifesciences.org/articles/98622T cellPIM kinaseproteomicsprotein translationIL-2IL-15 |
| spellingShingle | Julia M Marchingo Laura Spinelli Shalini Pathak Doreen A Cantrell PIM kinase control of CD8 T cell protein synthesis and cell trafficking eLife T cell PIM kinase proteomics protein translation IL-2 IL-15 |
| title | PIM kinase control of CD8 T cell protein synthesis and cell trafficking |
| title_full | PIM kinase control of CD8 T cell protein synthesis and cell trafficking |
| title_fullStr | PIM kinase control of CD8 T cell protein synthesis and cell trafficking |
| title_full_unstemmed | PIM kinase control of CD8 T cell protein synthesis and cell trafficking |
| title_short | PIM kinase control of CD8 T cell protein synthesis and cell trafficking |
| title_sort | pim kinase control of cd8 t cell protein synthesis and cell trafficking |
| topic | T cell PIM kinase proteomics protein translation IL-2 IL-15 |
| url | https://elifesciences.org/articles/98622 |
| work_keys_str_mv | AT juliammarchingo pimkinasecontrolofcd8tcellproteinsynthesisandcelltrafficking AT lauraspinelli pimkinasecontrolofcd8tcellproteinsynthesisandcelltrafficking AT shalinipathak pimkinasecontrolofcd8tcellproteinsynthesisandcelltrafficking AT doreenacantrell pimkinasecontrolofcd8tcellproteinsynthesisandcelltrafficking |