PIM kinase control of CD8 T cell protein synthesis and cell trafficking

Author:

Marchingo Julia M12ORCID,Spinelli Laura13ORCID,Pathak Shalini14ORCID,Cantrell Doreen A1ORCID

Affiliation:

1. Cell Signalling and Immunology Division, School of Life Sciences, University of Dundee

2. Blood Cells and Blood Cancer Division, Walter and Eliza Hall InsLtute of Medical Research

3. Molecular Cell and Developmental Biology Division, School of Life Sciences, University of Dundee

4. InnovaLon Factory Core Technology Facility, University of Manchester

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.

Publisher

eLife Sciences Publications, Ltd

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