Gastric epithelial cells drive retinoic acid biosynthesis in human gastric dendritic cells (MUC8P.803)

Abstract

Abstract Despite the high prevalence of chronic gastritis caused by H. pylori, the gastric mucosa as a unique immune environment has received little investigative attention. Here, we analyzed whether retinoic acid (RA), an important homeostatic factor in small intestine, also contributes to gastric immune regulation. Using HPLC, we detected both RA and the RA precursor molecule retinol in human gastric tissue, indicating that the gastric mucosa is an active site of RA biosynthesis. To determine the source of RA in gastric mucosa, we show that primary human gastric epithelial cells expressed RA biosynthesis genes Rdh10 and Aldh1a1, surprisingly at higher levels than small intestinal epithelial cells. Moreover, primary gastric epithelial cell cultures provided with retinol synthesized RA in vitro and induced the expression of the RA biosynthesis gene Aldh1a2 in co-cultured antigen-presenting cells through an RA-dependent mechanism, evidence that gastric epithelial cells confer the ability to generate RA to gastric DCs. Indeed, DCs purified from gastric mucosa had similar levels of aldehyde dehydrogenase activity and RA biosynthesis gene expression as small intestinal DCs, although gastric DCs lacked CD103. In summary, gastric epithelial cells have access to retinol, convert retinol to RA and drive RA biosynthesis in gastric DCs. Such RA biosynthesis capacity may enable gastric DCs to induce regulatory T cells and drive mucosal T cell homing during H. pylori infection.