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

Olivia J. James, Maud Vandereyken, Julia M. Marchingo, Francois Singh, Susan E. Bray, Jamie Wilson, Andrew G. Love and Mahima Swamy ()
Additional contact information
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

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: 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.

Date: 2021
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-24473-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24473-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-24473-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().