IL-15 and PIM kinases direct the metabolic programming of intestinal intraepithelial lymphocytes.

Autor: James OJ; MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, UK., Vandereyken M; MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, UK., Marchingo JM; Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dundee, UK., Singh F; MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, UK., Bray SE; NHS Research Scotland, Tayside Tissue Biorepository, University of Dundee, Dundee, UK., Wilson J; Department of Pathology, NHS Tayside, Ninewells Hospital, Dundee, UK., Love AG; MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, UK., Swamy M; MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, UK. m.swamy@dundee.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 Jul 13; Vol. 12 (1), pp. 4290. Date of Electronic Publication: 2021 Jul 13.
DOI: 10.1038/s41467-021-24473-2
Abstrakt: Intestinal intraepithelial lymphocytes (IEL) are an abundant population of tissue-resident T cells that protect and maintain the intestinal barrier. IEL respond to epithelial cell-derived IL-15, which is complexed to the IL-15 receptor α chain (IL-15/Rα). IL-15 is essential both for maintaining IEL homeostasis and inducing IEL responses to epithelial stress, which has been associated with Coeliac disease. Here, we apply quantitative mass spectrometry to IL-15/Rα-stimulated IEL to investigate how IL-15 directly regulates inflammatory functions of IEL. IL-15/Rα drives IEL activation through cell cycle regulation, upregulation of metabolic machinery and expression of a select repertoire of cell surface receptors. IL-15/Rα selectively upregulates the Ser/Thr kinases PIM1 and PIM2, which are essential for IEL to proliferate, grow and upregulate granzyme B in response to inflammatory IL-15. Notably, IEL from patients with Coeliac disease have high PIM expression. Together, these data indicate PIM kinases as important effectors of IEL responses to inflammatory IL-15.
(© 2021. The Author(s).)
Databáze: MEDLINE
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