tretinoin and Helicobacter-Infections

Dendritic cell (DC) expression of CD103, the α subunit of αEβ7 integrin, is thought to enable DC interactions with E-cadherin-expressing gastrointestinal epithelia for improved mucosal immunosurveillance. In the stomach, efficient DC surveillance of the epithelial barrier is crucial for the induction of immune responses to

Topics: Adult; Antigens, CD; Cadherins; Cell Adhesion; Cell Communication; Cells, Cultured; Dendritic Cells; Endosomes; Epithelial Cells; Gastric Mucosa; Healthy Volunteers; Helicobacter Infections; Helicobacter pylori; Humans; Immunity, Mucosal; Integrin alpha Chains; Primary Cell Culture; Tretinoin

Despite the high prevalence of chronic gastritis caused by Helicobacter pylori, the gastric mucosa has received little investigative attention as a unique immune environment. Here, we analyzed whether retinoic acid (RA), an important homeostatic factor in the small intestinal mucosa, also contributes to gastric immune regulation. We report that human gastric tissue contains high levels of the RA precursor molecule retinol (ROL), and that gastric epithelial cells express both RA biosynthesis genes and RA response genes, indicative of active RA biosynthesis. Moreover, primary gastric epithelial cells cultured in the presence of ROL synthesized RA in vitro and induced RA biosynthesis in co-cultured monocytes through an RA-dependent mechanism, suggesting that gastric epithelial cells may also confer the ability to generate RA on gastric dendritic cells (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 H. pylori-infected gastric mucosa, gastric RA biosynthesis gene expression was severely disrupted, which may lead to reduced RA signaling and thus contribute to disease progression. Collectively, our results support a critical role for RA in human gastric immune regulation.

Topics: Aldehyde Dehydrogenase; Animals; Coculture Techniques; Epithelial Cells; Female; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Immunity, Mucosal; Mice; Mice, Inbred C57BL; Monocytes; Primary Cell Culture; Tretinoin; Vitamin A