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Open AccessJournal ArticleDOI

The vagal innervation of the gut and immune homeostasis

Gianluca Matteoli, +1 more
- 01 Aug 2013 - 
- Vol. 62, Iss: 8, pp 1214-1222
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TLDR
The current understanding concerning the mechanisms and effects involved in the cholinergic anti-inflammatory pathway in the gastrointestinal tract is discussed, leading to the identification of new therapeutic targets to treat intestinal immune disease.
Abstract
The central nervous system interacts dynamically with the immune system to modulate inflammation through humoral and neural pathways. Recently, in animal models of sepsis, the vagus nerve (VN) has been proposed to play a crucial role in the regulation of the immune response, also referred to as the cholinergic anti-inflammatory pathway. The VN, through release of acetylcholine, dampens immune cell activation by interacting with α-7 nicotinic acetylcholine receptors. Recent evidence suggests that the vagal innervation of the gastrointestinal tract also plays a major role controlling intestinal immune activation. Indeed, VN electrical stimulation potently reduces intestinal inflammation restoring intestinal homeostasis, whereas vagotomy has the reverse effect. In this review, we will discuss the current understanding concerning the mechanisms and effects involved in the cholinergic anti-inflammatory pathway in the gastrointestinal tract. Deeper investigation on this counter-regulatory neuroimmune mechanism will provide new insights in the cross-talk between the nervous and immune system leading to the identification of new therapeutic targets to treat intestinal immune disease.

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Citations
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The gut as a sensory organ.

TL;DR: A major therapeutic opportunity exists to develop agents that target the receptors facing the gut lumen, and a major challenge is to develop a comprehensive understanding of the integrated responses of the gut to the sensory information it receives.
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Central Nervous System Control of Gastrointestinal Motility and Secretion and Modulation of Gastrointestinal Functions

TL;DR: The basic neural circuitry of extrinsic inputs to the GI tract as well as the major CNS nuclei that innervate and modulate the activity of these pathways are described.
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Innate immune responses to trauma

TL;DR: This Review aims to provide basic concepts about the posttraumatic response and is focused on the interactive events of innate immunity at frequent sites of injury: the endothelium at large, and sites within the lungs, inside and outside the brain and at the gut barrier.
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Autonomic Nervous System and Immune System Interactions

TL;DR: Both sympathetic and parasympathetic arms of the autonomic nervous system are instrumental in orchestrating neuroimmune processes, although additional studies are required to understand dynamic and complex adrenergic-cholinergic interactions.
References
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Journal ArticleDOI

Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin

TL;DR: Direct electrical stimulation of the peripheral vagus nerve in vivo during lethal endotoxaemia in rats inhibited TNF synthesis in liver, attenuated peak serum TNF amounts, and prevented the development of shock.
Journal ArticleDOI

The inflammatory reflex

Kevin J. Tracey
- 19 Dec 2002 - 
TL;DR: The discovery that cholinergic neurons inhibit acute inflammation has qualitatively expanded understanding of how the nervous system modulates immune responses, and the opportunity now exists to apply this insight to the treatment of inflammation through selective and reversible 'hard-wired' neural systems.
Journal ArticleDOI

Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation.

TL;DR: It is reported that the nicotinic acetylcholine receptor α7 subunit is essential for inhibiting cytokine synthesis by the cholinergic anti-inflammatory pathway.
Journal ArticleDOI

Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit.

TL;DR: This work has identified an acetylcholine-producing, memory phenotype T cell population in mice that is integral to the inflammatory reflex, and action potentials originating in the vagus nerve regulate T cells, which in turn produce the neurotransmitters required to control innate immune responses.
Journal ArticleDOI

Reflex control of immunity.

TL;DR: It might be possible to develop therapeutics that target neural networks for the treatment of inflammatory disorders, including the cholinergic anti-inflammatory pathway, that modulate immune responses and the progression of inflammatory diseases.
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