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Neural reflex pathways in intestinal inflammation: hypotheses to viable therapy
Rose A. Willemze, Misha D. Luyer, Wim A. Buurman and Wouter J. de Jonge
Abstract | Studies in neuroscience and immunology have clarified much of the anatomical and cellularbasis for bidirectional interactions between the nervous and immune systems. As with other organs, intestinalimmuneresponses and the development of immunity seems to be modulated by neural reflexes. Sympathetic immune modulation and reflexes are well described, and in the past decade the parasympathetic efferent vagus nerve has been added to this immune-regulation network. This system, designated the inflammatory reflex, comprises an afferent arm that senses inflammation and an efferent arm that inhibits innate immune responses. Intervention in this system as an innovative principle is currently being tested in pioneering trials of vagus nerve stimulation using implantable devices to treat IBD. Patients benefit from this treatment, but some of the working mechanisms remain to be established, for instance, treatment is effective despite the vagus nerve not always directly innervating the inflamed tissue. In this Review, we will focus on the direct neuronal regulatory mechanisms of immunity in the intestine, taking into account current advances regarding the innervation of the spleen and lymphoid organs, with a focus on the potential for treatment in IBD and other gastrointestinal pathologies.
Willemze, R. A. etal. Nat. Rev. Gastroenterol. Hepatol. 12, 353362 (2015); published online 12 May 2015; http://www.nature.com/doifinder/10.1038/nrgastro.2015.56
Web End =doi:10.1038/nrgastro.2015.56
Introduction
Neural mechanisms regulate all key functions of the gastro intestinal tract such as motility, secretion and vasoregulation (readers are referred to pertinent reviews, among others, on this topic1,2). The autonomic nervous system (ANS; see Box1 for a full list of glossary terms) acting largely autonomously in that its activities are not under direct conscious controlrepresents the extrinsic control of the intestine and is divided into sympathetic and parasympathetic branches. The ANS sympatheticand para sympathetic components originate in the central nervous system (CNS), with cell bodies in the brainstem and spinal cord, whereas the enteric nervous system (ENS) resides within the wall of the gastrointestinal tract. The ANS forms the major efferent component of the peripheral nervous system, containing integrative neuronal connections and even complete reflex arcs (neural pathways controlling a reflex action). Sympathetic preganglionic fibres originate from cholinergic neurons...