The oesophagus as an immune organ

The oesophagus has traditionally been viewed as a simple conduit for food transport. In performing this delivery function, it confronts a continuous influx of foreign antigens, including food particles with variable microbial content, and encounters many biophysical stimuli triggered by food textures and temperature. To meet these challenges, the oesophagus comprises a robust barrier featuring a thick, multilayered epithelium coated by mucins and mechanically held together by strong adhesion complexes, including desmosomal junctions. Sentinel immune cells, including a notable presence of CD8⁺ resident memory T cells, mast cells and dendritic cells, are abundant alongside IL-1 family cytokines released and activated under tight homeostatic regulation through a balance of proteases and antiproteases. Pattern recognition receptors, such as Toll-like receptors on epithelial cells, identify foreign antigens and can trigger cytokine release. Disruptions, whether acquired or genetically inherited, in these innate immune functions contribute to disease onset. Here, we present evidence that the oesophagus is an immune organ with extensive sensing properties designed to tolerate and mount defences against antigenic and biophysical challenges.