Abstract
Metaplasia in Barrett’s esophagus (BE) is characterized by the transition of squamous epithelium into intestinal-type columnar epithelium. The immune response in BE shares many similarities with the response found in the gut, which is different from the response found in a normal-looking esophagus. Here, we investigated the role of the genes associated with the retinoic acid (RA) pathway in BE, as RA is important not only in shaping the gut’s immune response but also in the induction of metaplasia in vitro. mRNA was isolated from esophageal and duodenal biopsies from BE (n = 14), reflux esophagitis patients (n = 9), and controls (n = 12). cDNA was made and qPCR was performed. The expression of RALDH1, CYP26A1, MAdCAM1 were similar for both the BE and duodenum, but different when compared to squamous esophageal epithelium. BE was characterized by a higher expression of RALDH2 and FOXP3, compared to the duodenum. In BE, RALDH2 correlated with expression of the myeloid dendritic cell-specific genes: CD11c and CD1c. Also, RALDH2 expression correlated with RAR-β and FOXP3. Hierarchical clustering on the expression of multiple relevant genes demonstrated that BE, duodenum, and SQ tissues are clustered as three different groups. The differential expression of RA-specific genes and dendritic cell (DC)-subsets indicates that BE resembles duodenal tissue. The higher expression of RALDH2 and FOXP3 in BE points at a mechanism associated with a possible anti-inflammatory microenvironment. This aberrant immune regulation might contribute to the altered tissue and immune responses found in BE.
Highlights
Barrett’s esophagus (BE) is characterized by a metaplasia from a multi-layered squamous epithelium into an intestinal-like, single-layered cylinder epithelium [1]
Expression of MAdCAM1 was low in squamous esophageal epithelium (SQ) obtained from the different patient groups (RE patients, BE patients, and controls; Figure 1A)
Expression of MAdCAM1 in SQ reflux esophagitis (RE), SQ from controls (SQ C), and inflamed tissue from RE (INFL RE) was significantly lower compared to the expression of MAdCAM1 in mRNA taken from biopsies of both the duodenum and BE (Figure 1A)
Summary
Barrett’s esophagus (BE) is characterized by a metaplasia from a multi-layered squamous epithelium into an intestinal-like, single-layered cylinder epithelium [1]. Patients with BE have an incidence rate of around 1 in 200 per patient-year to develop esophageal adenocarcinoma (EAC) [1]. The incidence of EAC continues to increase, and it is currently the fastest rising malignancy in the Western World [2]. It was shown that the immune cells found in BE and duodenal tissues are characterized by the presence of very similar T-cell phenotypes and a comparable expression of adhesion molecules, which is different from healthy esophageal tissue [3]. If expression levels of RA-pathway-specific genes are similar in BE and duodenal tissue, this would lead to a similar immune microenvironment
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