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

• Published in: The Journal of immunology (1950) Vol. 186; no. 4; pp. 2127 - 2137
• Main Authors: Verma, Saguna, Hoffmann, FuKun W, Kumar, Mukesh, Huang, Zhi, Roe, Kelsey, Nguyen-Wu, Elizabeth, Hashimoto, Ann S, Hoffmann, Peter R
• Format: Journal Article
• Language: English
• Published: United States 15-02-2011
• Subjects: 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; West Nile virus
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1002878

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.