Abstract
Over the past decades, there has been an increasing understanding of cellular and molecular mechanisms that mediate modulation of the immune system by the autonomic nervous system. The discovery that vagal nerve stimulation (VNS) attenuates endotoxin‐induced experimental sepsis paved the way for further studies investigating neuro‐immune interaction. In particular, great attention is now given to intestinal macrophages: several studies report the existence of both intrinsic and extrinsic neural mechanisms by which intestinal immune homoeostasis can be regulated in different layers of the intestine, mainly by affecting macrophage activation through neurotransmitter release. Given the important role of inflammation in numerous disease processes, such as inflammatory bowel disease (IBD), cholinergic anti‐inflammatory mechanisms are under intense investigation both from a basic and clinical science perspective in immune‐mediated diseases such as IBD. This review discusses recent insights on the cross‐talk between enteric neurons and the immune system, especially focusing on macrophages, and provides an overview of basic and translational aspects of the cholinergic anti‐inflammatory response as therapeutic alternative to reinstall immune homoeostasis in intestinal chronic inflammation.
Highlights
Over the past decades, there has been an increasing understanding of cellular and molecular mechanisms that mediate modulation of the immune system by the autonomic nervous system
Using anterograde tracers injected into the dorsal motor nucleus of the vagus (DMV), efferent vagal nerve terminals were shown to directly synapse with postganglionic neurons located in the enteric nervous system (ENS), rather than interacting with neurons in the prevertebral ganglia.[25,26]
The understanding of the pathogenesis of both Crohn's disease (CD) and ulcerative colitis (UC) has considerably increased over the last years
Summary
The implication of the autonomic nervous system (ANS), and of the parasympathetic innervation, as a key player in immune homoeostasis has increased exponentially. ACh acts as a mediator, interacting with α7 nicotinic acetylcholine receptors expressed by splenic macrophages.[21,22] In contrast to the initial hypothesis proposing direct contact between vagal nerve fibres and splenic Mφ,[23] it is clear that in the spleen, the vagus nerve rather indirectly modulates the innate immune response by activating adrenergic neurons in the paravertebral ganglia In line with this hypothesis, only in mice with an intact and innervated spleen, VNS is able to exert its anti‐inflammatory effect.[24] Given the central role of macrophages in a variety of intestinal diseases
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