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

Author

Listed:
  • Olivia J. James

    (University of Dundee)

  • Maud Vandereyken

    (University of Dundee)

  • Julia M. Marchingo

    (University of Dundee)

  • Francois Singh

    (University of Dundee)

  • Susan E. Bray

    (University of Dundee)

  • Jamie Wilson

    (Ninewells Hospital)

  • Andrew G. Love

    (University of Dundee)

  • Mahima Swamy

    (University of Dundee)

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.

Suggested Citation

  • Olivia J. James & Maud Vandereyken & Julia M. Marchingo & Francois Singh & Susan E. Bray & Jamie Wilson & Andrew G. Love & Mahima Swamy, 2021. "IL-15 and PIM kinases direct the metabolic programming of intestinal intraepithelial lymphocytes," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24473-2
    DOI: 10.1038/s41467-021-24473-2
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