Characterization of Immune Cell Populations and Acid-Sensing Receptors in the Human Esophagus

Abstract

Introduction: Esophageal inflammatory diseases are frequent diagnoses in clinical practice and have diverse etiologies, the most common being those associated with the exposure to gastric content, drugs and allergens. In diseases, the immunological component is well identified in endoscopic biopsies, which mainly contain the epithelium and the lamina propria; however, deeper layers are less studied. Moreover, the esophageal capacity of sensing luminal compounds is poorly understood. Methods: In transmural sections from proximal, middle and distal esophagus obtained from deceased patients, we performed a phenotypic analysis of the main immune cell populations and acid-sensing receptors by immunohistochemistry and immunofluorescence methods. Results: A total of nine donors were studied (absence of pathology, optimal tissue preservation and orientation). We found the following: (1) the vascular papillae and the lamina propria are the most infiltrated layers by the lymphoid lineage (T and B lymphocytes), followed by the epithelium, while the smooth muscular layers are mainly populated by the myeloid lineage (macrophages and mast cells); (2) intraepithelial macrophages are consistently found along the esophagus; and (3) eosinophils are absent in all the esophageal layers. The acid-sensing receptors ASIC-1, ASIC-2 and δENAC are expressed in the esophageal epithelium and in the lamina propria, yet only ASIC-2 is expressed in the muscularis mucosae. Conclusions: The human esophagus contains a differential distribution of immune cells and acid-sensing receptors across its layers. This study extends the esophageal histological knowledge previously described and reinforces its role as a defensive and sensing organ.