Selenoprotein K Knockout Mice Exhibit Deficient Calcium Flux in Immune Cells and Impaired Immune Responses

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 Ca2+ flux was decreased in T cells, neutrophils, and macrophages from Sel K-/- mice compared with controls. Ca2+-dependent functions including T cell proliferation, T cell and neutrophil migration, and Fcg 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 Ca2+ flux during immune cell activation and provide insight into molecular mechanisms by which dietary selenium enhances immune responses. The Journal of Immunology, 2011, 186: 2127-2137.