Selenoprotein K knockout mice exhibit deficient calcium flux in immune cells and impaired immune responses

J Immunol. 2011 Feb 15;186(4):2127-37. doi: 10.4049/jimmunol.1002878. Epub 2011 Jan 10.


Selenoprotein K (Sel K) is a selenium-containing protein for which no function has been identified. We found that Sel K is an endoplasmic reticulum transmembrane protein expressed at relatively high levels in immune cells and is regulated by dietary selenium. Sel K(-/-) mice were generated and found to be similar to wild-type controls regarding growth and fertility. Immune system development was not affected by Sel K deletion, but specific immune cell defects were found in Sel K(-/-) mice. Receptor-mediated Ca(2+) flux was decreased in T cells, neutrophils, and macrophages from Sel K(-/-) mice compared with controls. Ca(2+)-dependent functions including T cell proliferation, T cell and neutrophil migration, and Fcγ receptor-mediated oxidative burst in macrophages were decreased in cells from Sel K(-/-) mice compared with that in cells from controls. West Nile virus infections were performed, and Sel K(-/-) mice exhibited decreased viral clearance in the periphery and increased viral titers in brain. Furthermore, West Nile virus-infected Sel K(-/-) mice demonstrated significantly lower survival (2 of 23; 8.7%) compared with that of wild-type controls (10 of 26; 38.5%). These results establish Sel K as an endoplasmic reticulum-membrane protein important for promoting effective Ca(2+) flux during immune cell activation and provide insight into molecular mechanisms by which dietary selenium enhances immune responses.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Calcium / antagonists & inhibitors
  • Calcium / physiology*
  • Calcium Signaling / genetics*
  • Calcium Signaling / immunology*
  • Cell Migration Inhibition / genetics
  • Cell Migration Inhibition / immunology*
  • Disease Models, Animal
  • Endoplasmic Reticulum / immunology
  • Endoplasmic Reticulum / metabolism
  • Endoplasmic Reticulum / pathology
  • Gene Expression Regulation / immunology
  • Humans
  • Lymph Nodes / immunology
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / deficiency
  • Membrane Proteins / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Peritonitis / genetics
  • Peritonitis / immunology
  • Peritonitis / pathology
  • Receptors, Peptide / metabolism
  • Selenium / administration & dosage
  • Selenium / physiology
  • Selenoproteins / biosynthesis
  • Selenoproteins / deficiency*
  • Selenoproteins / genetics*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology


  • KDELR1 protein, human
  • Membrane Proteins
  • Receptors, Peptide
  • Selenoproteins
  • Selenium
  • Calcium