Cholinergic Modulation of Epithelial Barrier Function in Peyer’s Patch Follicle-Associated Epithelium: An Ex Vivo Electrophysiological Study

Background: Peyer's patches represent highly specialized GALT that plays a key role in mucosal immune surveillance. FAE covering Peyer's patches differs structurally and functionally from the adjacent villous epithelium; however, regulation of its barrier function by cholinergic signaling remains poorly understood. Methods: Ex vivo, electrophysiological recordings were done with Peyer’s patch FAE isolated from the small intestine of male Wistar rats using the Ussing chamber technique. TER was recorded over a period of 70 minutes under control conditions, following the administration of acetylcholine, nicotinic receptor blockade using Mec, and combined treatment. Results: Control tissues exhibited a time-dependent progressive decline in TER. Blockade of nicotinic receptors with Mec significantly reduced TER, consistent with a contribution of endogenous cholinergic tone to barrier maintenance. Ach alone failed to produce a statistically significant alteration in TER. The combination of Ach and Mec produced an attenuated response compared to Mec alone, consistent with an interaction between cholinergic stimulation and receptor blockade in regulating epithelial barrier dynamics. Conclusions: These data provide evidence that cholinergic signaling regulates epithelial barrier function in Peyer’s patch FAE in a context-dependent manner. The different responses to Ach and nicotinic receptor inhibition underline the unique physiological properties of this specialized epithelium and point toward non-neuronal cholinergic pathways as modulators of the immune-epithelial interface in the gut.