Dendritic Cell-Associated Immune Inflammation of Cardiac Mucosa: A Possible Factor in the Formation of Barrett’s Esophagus

Abstract

Background The development of Barrett's esophagus is poorly understood, but it has been suggested that cardiac mucosa is a precursor of intestinal type metaplasia and that inflammation of cardiac mucosa may play a role in the formation of Barrett's esophagus. The present study was undertaken to examine the presence and distribution of immune-inflammatory cells in cardiac mucosa, specifically focusing on dendritic cells because of their importance as regulators of immune reactions. Material and Methods Endoscopic biopsy specimens were obtained from 12 patients with cardiac mucosa without Barrett's esophagus or adenocarcinoma and from 21 patients with Barrett's esophagus without dysplasia (intestinal metaplasia). According to histology, in nine of the 21 specimens with Barrett's esophagus, areas of mucosa composed of cardiac type epithelium-lined glands were present as well. Immunohistochemical staining and electron microscopy were used to examine immune-inflammatory cells in paraffin-embedded sections. Results Immune-inflammatory cells, including T cells, B cells, dendritic cells, macrophages, and mast cells, were present in the connective tissue matrix that surrounded cardiac type epithelium-lined glands in all patients with cardiac mucosa. Clustering of dendritic cells with each other and with lymphocytes and the intrusion of dendritic cells between glandular mucus cells were observed. In the Barrett's esophagus specimens that contained cardiac type glands, computerized CD83 expression quantitation revealed that there were more dendritic cells in cardiac mucosa than in intestinal metaplasia. Conclusion Immune-inflammatory infiltrates containing dendritic cells are consistently present in cardiac mucosa. The finding of a larger number of dendritic cells in areas of cardiac mucosa in Barrett's esophagus biopsies suggests that the immune inflammation of cardiac mucosa might play a role in modifying the local tissue environment to promote the development of specialized intestinal type metaplasia.

The interplay between surfaces and soluble factors define the immunologic and angiogenic properties of myeloid dendritic cells

“…Thus, in order to design DC-based vaccines or treatments focused on changing the phenotype of DCs associated with diseases, such as cancer [68-70] or atherosclerosis [71,72] among others, it becomes necessary to fully investigate the microenvironment in which these cells are present or will be delivered.…”

Barrett’s to Oesophageal Cancer Sequence: A Model of Inflammatory-Driven Upper Gastrointestinal Cancer

“…Immune cell infiltration is observed during all stages of the progression from BO to dysplasia to OAC, although there is still a lack of significant research into the roles that they play in oesophageal disease. Dendritic cells (DCs) have been shown to be increased in BO tissue compared with normal oesophageal tissue [10]; DCs may also play a role in progression to cancer, as they are found at greater density in OAC than in BO, often in clusters with T and B cells in the lamina propria [11]. Although the role of DCs remains unclear, an intriguing proposal is that DCs in the oesophageal microenvironment may activate dormant stem cells, identified by the stem cell marker Musashi-1, causing the development of BO and OAC [12].…”

Chemokine-mediated distribution of dendritic cell subsets in renal cell carcinoma

“…The infiltration of DCs into some primary tumour types has been found to be associated with significantly improved patient survival and a reduced incidence of recurrent disease [11,12]. It is known that tumours avoid surveillance by the immune system through various mechanisms, including the inhibition of the recruitment of DCs at the tumour site, as well as impairment of function of DCs by local production of immunosuppressive cytokines [13].…”