Selenoproteins Regulate Macrophage Invasiveness and Extracellular Matrix-related Gene Expression

Abstract

Background: Selenium, a micronutrient whose deficiency in diet causes immune dysfunction and inflammatory disorders, is thought to exert its physiological effects mostly in the form of selenium-containing proteins (selenoproteins). Incorporation of selenium into the amino acid selenocysteine (Sec), and subsequently into selenoproteins is mediated by (Sec) (tRNA^{[Ser]Sec}). Results: To define macrophage-specific selenoprotein functions, we generated mice with the (Sec) (tRNA^{[Ser]Sec}) gene specifically deleted in myeloid cells. These mutant mice were devoid of the "selenoproteome" in macrophages, yet exhibited largely normal inflammatory responses. However, selenoprotein deficiency led to aberrant expression of extracellular matrix-related genes, and diminished migration of macrophages in a protein gel matrix. Conclusion: Selenium status may affect immune defense and tissue homeostasis through its effect on selenoprotein expression and the trafficking of tissue macrophages.