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IL-15 and PIM kinases direct the metabolic programming of intestinal intraepithelial lymphocytes.
James, Olivia J; Vandereyken, Maud; Marchingo, Julia M; Singh, Francois; Bray, Susan E; Wilson, Jamie; Love, Andrew G; Swamy, Mahima.
Afiliación
  • James OJ; MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, UK.
  • Vandereyken M; MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, UK.
  • Marchingo JM; Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dundee, UK.
  • Singh F; MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, UK.
  • Bray SE; NHS Research Scotland, Tayside Tissue Biorepository, University of Dundee, Dundee, UK.
  • Wilson J; Department of Pathology, NHS Tayside, Ninewells Hospital, Dundee, UK.
  • Love AG; MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, UK.
  • Swamy M; MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, UK. m.swamy@dundee.ac.uk.
Nat Commun ; 12(1): 4290, 2021 07 13.
Article en En | MEDLINE | ID: mdl-34257288
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Interleucina-15 Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Interleucina-15 Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article Pais de publicación: Reino Unido