Lack of Mucosal Cholinergic Innervation Is Associated With Increased Risk of Enterocolitis in Hirschsprung's Disease.

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Etat: Public
Version: de l'auteur⸱e
Licence: CC BY-NC-ND 4.0
ID Serval
serval:BIB_DF06809C98AD
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Lack of Mucosal Cholinergic Innervation Is Associated With Increased Risk of Enterocolitis in Hirschsprung's Disease.
Périodique
Cellular and molecular gastroenterology and hepatology
Auteur⸱e⸱s
Keck S., Galati-Fournier V., Kym U., Moesch M., Usemann J., Müller I., Subotic U., Tharakan S.J., Krebs T., Stathopoulos E., Schmittenbecher P., Cholewa D., Romero P., Reingruber B., Bruder E., Group N.S., Holland-Cunz S.
ISSN
2352-345X (Electronic)
ISSN-L
2352-345X
Statut éditorial
Publié
Date de publication
2021
Peer-reviewed
Oui
Volume
12
Numéro
2
Pages
507-545
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Hirschsprung's disease (HSCR) is a congenital intestinal motility disorder defined by the absence of enteric neuronal cells (ganglia) in the distal gut. The development of HSCR-associated enterocolitis remains a life-threatening complication. Absence of enteric ganglia implicates innervation of acetylcholine-secreting (cholinergic) nerve fibers. Cholinergic signals have been reported to control excessive inflammation, but the impact on HSCR-associated enterocolitis is unknown.
We enrolled 44 HSCR patients in a prospective multicenter study and grouped them according to their degree of colonic mucosal acetylcholinesterase-positive innervation into low-fiber and high-fiber patient groups. The fiber phenotype was correlated with the tissue cytokine profile as well as immune cell frequencies using Luminex analysis and fluorescence-activated cell sorting analysis of colonic tissue and immune cells. Using confocal immunofluorescence microscopy, macrophages were identified in close proximity to nerve fibers and characterized by RNA-seq analysis. Microbial dysbiosis was analyzed in colonic tissue using 16S-rDNA gene sequencing. Finally, the fiber phenotype was correlated with postoperative enterocolitis manifestation.
The presence of mucosal nerve fiber innervation correlated with reduced T-helper 17 cytokines and cell frequencies. In high-fiber tissue, macrophages co-localized with nerve fibers and expressed significantly less interleukin 23 than macrophages from low-fiber tissue. HSCR patients lacking mucosal nerve fibers showed microbial dysbiosis and had a higher incidence of postoperative enterocolitis.
The mucosal fiber phenotype might serve as a prognostic marker for enterocolitis development in HSCR patients and may offer an approach to personalized patient care and new therapeutic options.
Mots-clé
Cholinergic nerve fibers, Enterocolitis, Macrophages, Microbiome, Neuroimmunology, Th17 cells, Cholinergic Nerve Fibers, Th17 Cells
Pubmed
Web of science
Open Access
Oui
Création de la notice
30/03/2021 13:09
Dernière modification de la notice
28/10/2021 5:45
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