Proteomics

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Comprehensive proteomics analyses of IL-15 driven activation of intestinal intraepithelial lymphocytes


ABSTRACT: Intestinal intraepithelial lymphocytes (IEL) are an abundant population of tissue-resident T cells that protect the gut from pathogens and maintain intestinal homeostasis. The cytokine IL-15 is trans-presented by epithelial cells to IEL in complex with the IL-15 receptor α chain (IL-15Rα) and plays essential roles both in maintaining IEL homeostasis, and in inducing IEL activation in response to epithelial stress. When overproduced, IL-15 is a key driver of the gluten-induced enteropathy Coeliac disease, through cytotoxic activation of IEL. To better understand how IL-15 directly regulates both homeostatic and inflammatory functions of IEL, we performed quantitative proteomics of IL-15/Rα-stimulated murine IEL, sorted into their 3 main subpopulations, TCRγδ CD8αα, TCRαβ CD8αβ and TCRαβ CD8αα expressing IEL. The data reveal that high IL-15/Rα stimulation licenses cell cycle activation, upregulates the biosynthetic machinery in IEL, increases mitochondrial respiratory capacity and induces expression of cell surface immune receptors and adhesion proteins that potentially drive IEL activation.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): T Cell, Small Intestine

DISEASE(S): Celiac Disease

SUBMITTER: Renata Soares  

LAB HEAD: Mahima Swamy

PROVIDER: PXD025891 | Pride | 2021-05-10

REPOSITORIES: Pride

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Publications

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

James Olivia J OJ   Vandereyken Maud M   Marchingo Julia M JM   Singh Francois F   Bray Susan E SE   Wilson Jamie J   Love Andrew G AG   Swamy Mahima M  

Nature communications 20210713 1


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  ...[more]

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