Work

Immunoregulatory roles of the enteric nervous system in esophageal motility control: mechanisms, advances, and therapeutic potential

Year: 2026

Type: review

Abstract: The maintenance of esophageal motility relies on the coordinated actions of the mucosa, nervous system, and muscular layers. The mucosal layer not only serves as a physical barrier but also functions as a sensory interface that detects intraluminal stimuli and contributes to local regulation through the release of bioactive molecules. As the central regulatory component, the nervous system comprises an integrated network formed by the intrinsic enteric nervous system and the extrinsic sympathetic and parasympathetic nervous systems, which collectively integrate afferent signals and coordinate muscular activity. Immune mechanisms also play an important modulatory role in the regulation of esophageal motility. Immune cells, including mast cells, eosinophils, T cells, and macrophages, engage in bidirectional interactions with neuropeptides and the esophageal microbiota, thereby contributing to motility regulation through immune-neural interactions. The muscular layer, composed of striated and smooth muscle, serves as the effector component of motility, with the rhythm and intensity of contraction determining the efficiency of esophageal propulsion and clearance. Accordingly, with esophageal motility as its central focus, this review examines the interactions and coordination among the esophageal mucosa, nervous system, and musculature. Based on a systematic review of recent studies investigating the microscopic regulation of neural and muscular function by neurotransmitters, immune cells, sensory nerve endings, and metabolites derived from the esophageal microbiota, this review elucidates the critical role of the nervous system, particularly the enteric nervous system, in linking mucosal signals to muscular responses, together with its associated immunoregulatory mechanisms. It further explores how these components act synergistically to maintain normal esophageal motility and provides a theoretical basis for pathophysiological research into esophageal motility disorders.

Source: Frontiers in Immunology

DOI: 10.3389/fimmu.2026.1987626