The Expression of RALDH Enzymes by Small Intestinal Epithelial Cells

Abstract

Retinal dehydrogenase (RALDH) is the key enzyme that regulates the production of retinoic acid (RA), an important mediator of immune responses in the gut. RA is the biologically active metabolite of vitamin A. Vitamin A is at the same time processed and metabolized in small intestine. RA produced by intestinal epithelial cells is known to be essential for the induction of characteristic mucosal immune responses by innate immune cells in the intestinal environment. The expression of RALDH enzymes is tissue-specific, with certain tissues expressing higher concentrations than others, and with variations between the different isoforms of the enzyme. RALDH levels and RA production by the innate immune cells in the gut have been shown to be regulated by dietary vitamin A. However the expression of RALDH enzymes in the intestinal epithelium does not decrease with different levels of vitamin A in the diet. In the case of RALDH3 it is even up-regulated in mice fed vitamin A deficient diets. It is believed that this is due to a compensatory mechanism. In this review we look at the genetic and environmental factors that can affect the expression of this enzyme in small intestinal epithelial cells. From this perspective we point at the possible indirect effects that these factors could have on the innate immune cells in the gut through its effects on the production on RA by intestinal epithelial cells.