Cholinergic regulation on polymeric immunoglobulin receptor expression in Caco-2 cells

The polymeric immunoglobulin receptor (pIgR) mediates trans cytosis of IgA, a pivotal anti-inflammatory player of the mucosal immune system. Transcytosis mediated by pIgR entails protein effectors of vesicle-mediated transport involved in signal pathway activation that lead to the sorting of pIgR-IgA complexes from the basolateral to apical membrane. Each step of pIgR transport encompasses multiple targets for regulation, but the role of cholinergic system components, i.e. acetylcholine (ACh), the ligand of nicotinic (nAChR) and muscarinic (mAChR) receptors, is unclear. This study evaluated the effect of the cholinergic system on pIgR at transcriptional and protein levels. Accordingly, lipopolysaccharide (LPS)-primed Caco-2 cells were treated with nicotine (nAChR agonist) and/or mecamylamine (nAChR antagonist) or with muscarine (mAChR agonist) and/ or atropine (mAChR antagonist), and then pIgR was analysed in situ by immunofluorescence and by RT-qPCR. In general terms, cholinergic antagonists counteracted the upmodu latory outcome of both cholinergic agonists on both pIgR cellular location and mRNA levels. These findings suggest that the cholinergic system plays a key role in the regulation of epithelial immunity by modulating pIgR expression. The study provides insights into the interaction between the cholinergic system and intestinal immune mechanisms for future research in mucosal immunity and possible therapeutic strategies.