Once seen as a simple food passageway, the esophagus is now recognized as a dynamic immune organ.
Its stratified squamous epithelium forms a tough barrier, reinforced by mucins and unique processes like citrullination.
A distinct early-life microbiome shapes epithelial development and immune responses. Key players include pattern recognition receptors, IL-1 family cytokines (IL-33, TSLP), a carefully balanced protease–antiprotease system, and neuroimmune circuits that link sensation, immunity, and barrier control.
Genetic variants (e.g., in TSLP, CAPN14, FLG, SPINK5) increase vulnerability to environmental triggers, driving diseases like eosinophilic esophagitis (EoE) and GERD through barrier breakdown and chronic inflammation.
This new understanding is fueling targeted therapies - immune modulation, barrier repair, and cytokine blockers- while opening research avenues in microbiome-immune crosstalk, single-cell profiling, and precision medicine for allergic, inflammatory, and neoplastic esophageal conditions.
In short: the esophagus actively senses the environment and maintains mucosal peace through sophisticated immune networks. Unlocking these mechanisms promises better treatments for challenging esophageal diseases.
References:
https://www.jacionline.org/article/S0091-6749(25)01184-4/fulltext