The Oesophagus: Not Just a Food Pipe But An Immune Organ The oesophagus has long been viewed as a simple food pipe, transporting material from the mouth to the stomach. A recent publication in Nature Reviews Gastroenterology & Hepatology presents a new perspective: the oesophagus is also an immunological organ, playing a critical role in maintaining homeostasis and immune tolerance to food. Researchers from Cincinnati Children’s Hospital, led by Prof. Marc Rothenberg, synthesised two decades of work from the CURED Lab, including genetic studies, to show that the oesophagus possesses extensive sensing properties that enable it to tolerate and defend against antigenic and biophysical challenges. Prof. Marc Rothenberg, director of the Division of Allergy and Immunology, Cincinnati Center for Eosinophilic Diseases, and the principal investigator at the Consortium of the Eosinophilic Gastrointestinal Disease Researchers, generally known as CEGIR. “This publication synthesizes two decades of research from my lab, which has led me to propose that the esophagus should be considered as an immunological organ. When I first learned about the esophagus in medical school, it was considered a simple conduit for transporting food from the mouth to the stomach. However, there is now compelling evidence that the esophagus has a critical role in maintaining homeostasis, including immune tolerance to food, and that perturbations in its innate function can lead to a variety of diseases, most convincingly eosinophilic esophagus.” Source Key findings Barrier function: The oesophagus features a multilayered epithelium coated by unique mucins and microbiota, mechanically held together by strong adhesion complexes, including desmosomal junctions. Immune cells: Sentinel immune cells, including a notable presence of mast cells, tissue-resident CD8+T cells and dendritic cells, are abundant, highlighting their role as an immune surveillance site. Cytokines and proteases: IL-1 family cytokines are released and activated under tight homeostatic regulation through a balance of proteases and antiproteases. This ensures cytokines are only active when truly needed, preventing unnecessary inflammation or immune responses. Sensing mechanisms: Pattern-recognition receptors (such as toll-like receptors, TLRs) on epithelial cells and infiltrating nerves, identify foreign antigens and pathogenic insults and can trigger acute and chronic immune responses. Clinical implications Disruptions of these immune functions, whether by genetic variants or acquired factors, play a key role in the pathogenesis of conditions such as Eosinophilic Oesophagitis (EoE), gastro-oesophageal reflux disease (GERD) and oesophageal cancer. In EoE, eosinophils infiltrate tissue where they are not normally present. Yet their depletion does not consistently improve symptoms, suggesting they may also play regulatory roles. Conclusions Taken together, these data indicate that the traditional view of the oesophagus as a mere conduit underestimates its complexity. The evidence supports recognising the oesophagus as a component of the innate immune system, with perturbations contributing to a spectrum of diseases. Reference: Rochman, M., Kellerman, K., Jankowski, M.P. and Rothenberg, M.E., 2025. The oesophagus as an immune organ. Nature Reviews Gastroenterology & Hepatology, 22(9), pp.657–667. doi:10.1038/s41575-025-01086-4. Read similar news: Types of Eosinophilic Diseases What is the role of the microbiome in EGIDs? Insights from EoE Genetic Research by Molly Shook A New Study on Early Life Exposures as Risk Factors for Non-EoE EGIDs Gut Microbes Linked to Long-Term Allergies by Affecting Immune Cells and IgE Production Eosinophilic Diseases Research: Past, Present and Future EoE Position Paper: Global Advocacy For Better EoE Care Medical Guidelines Manage Cookie Preferences