Outcomes of nicotinic modulation on markers of intestinal IgA antibody response.

Abstract

Acetylcholine (ACh), as a ligand of nicotinic acetylcholine receptors (nAChRs), plays a key role in the cholinergic anti-inflammatory pathway; however, its role in the immunoglobulin A (IgA) response remains unknown. Therefore, the present study aimed to investigate the role of ACh in the intestinal biomarkers involved in IgA synthesis and the polymeric immunoglobulin receptor (pIgR) involved in IgA transcytosis. Groups of mice were administered GTS-21 (an α7nAChR agonist) or mecamylamine (a non-selective nAChR antagonist) intraperitoneally for 7 days. Intestinal fluids were used for antibody concentration assessment by ELISA, cell suspensions from Peyer's patches and the lamina propria were obtained for flow cytometric analysis of plasma cells, and CD4⁺ T-cells expressing intracellular transforming growth factor (TGF)-β and IgA-producing interleukin (IL)-4, -5, -6 and -10, and isolated epithelial cells to determine the levels of pIgR mRNA using reverse transcription-quantitative PCR. Regarding to the untreated control group, the concentration of IgA was reduced in the mecamylamine group and unaltered in the GTS-21 group while IgM levels exhibited no differences; the percentage of IgA⁺ plasma cells from Peyer's patches and the lamina propria, and the percentage of TGF-β⁺/CD4⁺ T-cells from Peyer's patches were greater in the GTS-21-group. In both treatment groups, the percentages of IgM⁺ plasma cells and IL-6⁺/IL-10⁺ CD4⁺ T cells were greater in both compartments; pIgR mRNA expression levels decreased in epithelial cells. The percentage of IL-4 CD4⁺ T-cells were greater in Peyer's patches and lower in the lamina propria in the mecamylamine group, and the percentage of IL-5 CD4⁺ T-cells in the lamina propria were decreased in both treatment groups. These findings require further examination to address the impact of cholinergic modulation on IgA-transcytosis via pIgR. The present study may be an experimental reference for clinical trials that address the role of nicotinic system in intestinal dysfunctions as postoperative ileus.