James 2021 Nat Commun
| 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. |
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
