James 2021 Nat Commun

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James OJ, Vandereyken M, Marchingo JM, Singh F, Bray SE, Wilson J, Love AG, Swamy M (2021) IL-15 and PIM kinases direct the metabolic programming of intestinal intraepithelial lymphocytes. Nat Commun 12:4290.

» PMID: 34257288 Open Access

James Olivia J, Vandereyken Maud, Marchingo Julia M, Singh Francois, Bray Susan E, Wilson Jamie, Love Andrew G, Swamy Mahima (2021) Nat Commun

Abstract: 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.

Bioblast editor: Reiswig R


Labels: MiParea: Respiration, nDNA;cell genetics 


Organism: Mouse  Tissue;cell: Lymphocyte  Preparation: Permeabilized cells, Intact cells 


Coupling state: LEAK, ROUTINE, OXPHOS, ET  Pathway: N, S, NS, ROX  HRR: Oxygraph-2k 

2021-08