Figure 4.

The parasympathetic nervous system-mediated anti-inflammatory reflex. Vagal afferents respond to inflammation mediators and send signals to the brainstem, where a signal is produced and transmitted by vagal efferents to the splenic nerve, causing noradrenaline (NA) release in the spleen. CD4+ T lymphocytes, which express the β2- adrenaline receptor (β2AR), uptake NA and release acetylcholine (ACh). Acetylcholine inhibits the synthesis of proinflammatory cytokines in the macrophages that express the α7nAChR receptor (α7 nicotinic acetylcholine receptors). Further, the anti-inflammatory reflex diminishes CD11b expression on neutrophils, augments the release of pro-resolving mediators (SPMs), and reduces antibody secretion and migration of B lymphocytes. In the intestine, ACh stimulates antigen-presenting cells (APCs) through muscarinic receptors (mAChR), contributing to the maintenance of regulatory T cells (Treg). With permission from Ref. [67].