Neuronal regulation of the gut immune system and neuromodulation for treating inflammatory bowel disease

Populin, Luis C.; Stebbing, Margaret Susanne; Furness, John B.

doi:10.1096/fba.2021-00070

Cited by 33 publications

(20 citation statements)

References 106 publications

(273 reference statements)

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“…Reductions in enteric cholinergic innervation of the gut mucosa and serotonin production have been found in HAEC patients [ 21 , 22 , 47 ]. It is now recognised that the ENS communicates with the gut immune system and has an important role in immune activation and suppression [ 48 , 49 , 50 ]. There are many pathways involved in this communication [ 49 , 51 ], and also reciprocal interaction where the immune system influences ENS function [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

“…It is now recognised that the ENS communicates with the gut immune system and has an important role in immune activation and suppression [ 48 , 49 , 50 ]. There are many pathways involved in this communication [ 49 , 51 ], and also reciprocal interaction where the immune system influences ENS function [ 52 ]. Recent data shows that enteric glia also play important roles in this exchange [ 53 , 54 ].…”

Section: Discussionmentioning

confidence: 99%

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A Novel Method for Identifying the Transition Zone in Long-Segment Hirschsprung Disease: Investigating the Muscle Unit to Ganglion Ratio

et al. 2022

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Hirschsprung disease (HSCR) is characterised by the absence of enteric ganglia along variable lengths of the distal bowel. Current gold standard treatment involves the surgical resection of the defective, aganglionic bowel. Clear and reliable distinction of the normoganglionated bowel from the transition zone is key for successful resection of the entire defective bowel, and the avoidance of subsequent postoperative complications. However, the intraoperative nature of the tissue analysis and the variability of patient samples, sample preparation, and operator objectivity, make reproducible identification of the transition zone difficult. Here, we have described a novel method for using muscle units as a distinctive landmark for quantifying the density of enteric ganglia in resection specimens from HSCR patients. We show that the muscle unit to ganglion ratio is greater in the transition zone when compared with the proximal, normoganglionated region for long-segment HSCR patients. Patients with short-segment HSCR were also investigated, however, the muscle unit to ganglion ratio was not significantly different in these patients. Immunohistochemical examination of individual ganglia showed that there were no differences in the proportions of either enteric neurons or glial cells through the different regions of the resected colon. In addition, we identified that the size of enteric ganglia was smaller for patients that went on to develop HSCR associated enterocolitis; although the density of ganglia, as determined by the muscle unit to ganglia ratio, was not different when compared with patients that had no further complications. This suggests that subtle changes in the enteric nervous system, even in the “normoganglionated” colon, could be involved in changes in immune function and subsequent bacterial dysbiosis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A Novel Method for Identifying the Transition Zone in Long-Segment Hirschsprung Disease: Investigating the Muscle Unit to Ganglion Ratio

et al. 2022

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“…Extrinsic nociceptor neurons have recently been shown to mediate a protective immune response against Salmonella infection through direct sensing and release of calcitonin-gene-related peptide, which suppresses M-cell density and maintains segmental filamentous bacterial colonization of the ileum [ 38 ]. It has also been proposed that enteral sympathetic neurons are involved in the first stage of prions’ neuronal invasion, and that their associated neurons are potential prion carriers in the central nervous system [ 39 , 40 ].…”

Section: Innervation and Vascularization Of Isolated Lymphoid Folliclesmentioning

confidence: 99%

Colitis and Colorectal Carcinogenesis: The Focus on Isolated Lymphoid Follicles

2022

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Gut-associated lymphoid tissue is one of the most diverse and complex immune compartments in the human body. The subepithelial compartment of the gut consists of immune cells of innate and adaptive immunity, non-hematopoietic mesenchymal cells, and stem cells of different origins, and is organized into secondary (and even tertiary) lymphoid organs, such as Peyer’s patches, cryptopatches, and isolated lymphoid follicles. The function of isolated lymphoid follicles is multifaceted; they play a role in the development and regeneration of the large intestine and the maintenance of (immune) homeostasis. Isolated lymphoid follicles are also extensively associated with the epithelium and its conventional and non-conventional immune cells; hence, they can also function as a starting point or maintainer of pathological processes such as inflammatory bowel diseases or colorectal carcinogenesis. These relationships can significantly affect both physiological and pathological processes of the intestines. We aim to provide an overview of the latest knowledge of isolated lymphoid follicles in colonic inflammation and colorectal carcinogenesis. Further studies of these lymphoid organs will likely lead to an extended understanding of how immune responses are initiated and controlled within the large intestine, along with the possibility of creating novel mucosal vaccinations and ways to treat inflammatory bowel disease or colorectal cancer.

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“…Sympathetic input suppresses colon motility by acting on intrinsic myenteric neurons while regulates gut immune function through releasing noradrenaline that acts on G-protein-coupled α and β adrenergic receptors expressed by enteric neurons and immune cells ( Populin et al, 2021 ; Smith-Edwards et al, 2021 ). The vagus nerve, on the other hand, modulates intestinal inflammation through the key mediator of the cholinergic anti-inflammatory pathway, acetylcholine (ACh), acting primarily on nAChRs and driving Na + influx and membrane depolarization ( Van Der Zanden et al, 2009a ), regulating cytokine release from immune cells ( Rueda Ruzafa et al, 2021 ).…”

Section: Ion Channels In Intestinal Neuroimmune Interactionsmentioning

confidence: 99%

Ion channel regulation of gut immunity

Feng

Xie

2022

Journal of General Physiology

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Mounting evidence indicates that gastrointestinal (GI) homeostasis hinges on communications among many cellular networks including the intestinal epithelium, the immune system, and both intrinsic and extrinsic nerves innervating the gut. The GI tract, especially the colon, is the home base for gut microbiome which dynamically regulates immune function. The gut’s immune system also provides an effective defense against harmful pathogens entering the GI tract while maintaining immune homeostasis to avoid exaggerated immune reaction to innocuous food and commensal antigens which are important causes of inflammatory disorders such as coeliac disease and inflammatory bowel diseases (IBD). Various ion channels have been detected in multiple cell types throughout the GI tract. By regulating membrane properties and intracellular biochemical signaling, ion channels play a critical role in synchronized signaling among diverse cellular components in the gut that orchestrates the GI immune response. This work focuses on the role of ion channels in immune cells, non-immune resident cells, and neuroimmune interactions in the gut at the steady state and pathological conditions. Understanding the cellular and molecular basis of ion channel signaling in these immune-related pathways and initial testing of pharmacological intervention will facilitate the development of ion channel–based therapeutic approaches for the treatment of intestinal inflammation.

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Neuronal regulation of the gut immune system and neuromodulation for treating inflammatory bowel disease

Abstract: This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as

Cited by 33 publications

References 106 publications

A Novel Method for Identifying the Transition Zone in Long-Segment Hirschsprung Disease: Investigating the Muscle Unit to Ganglion Ratio

A Novel Method for Identifying the Transition Zone in Long-Segment Hirschsprung Disease: Investigating the Muscle Unit to Ganglion Ratio

Colitis and Colorectal Carcinogenesis: The Focus on Isolated Lymphoid Follicles

Ion channel regulation of gut immunity

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