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Harnessing the small intestinal axis to resolve systemic inflammation

This Perspective presents the potential of the Small Intestinal Axis, a sub-division of the Gut-immune Axis, to modulate systemic inflammation based on sensing contents of the gut lumen. Gut mucosal immunity regulates tolerance to food and gut contents and is a significant factor in maintaining syst...

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Detalles Bibliográficos
Autores principales: Bodmer, Mark, Itano, Andrea, McInnes, Iain
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9706197/
https://www.ncbi.nlm.nih.gov/pubmed/36458009
http://dx.doi.org/10.3389/fimmu.2022.1060607
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author Bodmer, Mark
Itano, Andrea
McInnes, Iain
author_facet Bodmer, Mark
Itano, Andrea
McInnes, Iain
author_sort Bodmer, Mark
collection PubMed
description This Perspective presents the potential of the Small Intestinal Axis, a sub-division of the Gut-immune Axis, to modulate systemic inflammation based on sensing contents of the gut lumen. Gut mucosal immunity regulates tolerance to food and gut contents and is a significant factor in maintaining systemic homeostasis without compromising immunity to pathogens. This is achieved through anatomical structures and signaling pathways that link the tolerogenic potential of the proximal small intestine to systemic immunity. Non-live preparations of microbes isolated from human small intestinal mucosa, and the extracellular vesicles (EVs) which they shed, can resolve systemic inflammation without systemic exposure after oral delivery. The mechanism involves primary interactions with pattern recognition receptors followed by trafficking of immune cells through mesenteric lymph nodes. This generates in the periphery a population of circulating CD4(+) T cells which have regulatory function but an atypical FoxP3(-) phenotype. There is no modification of the resident gut microbiome. Discoveries using this novel approach of targeting mucosal microbial elements to the tolerogenic proximal regions of the small intestine are revealing some of the mysteries of the relationship between the gut and immune system.
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spelling pubmed-97061972022-11-30 Harnessing the small intestinal axis to resolve systemic inflammation Bodmer, Mark Itano, Andrea McInnes, Iain Front Immunol Immunology This Perspective presents the potential of the Small Intestinal Axis, a sub-division of the Gut-immune Axis, to modulate systemic inflammation based on sensing contents of the gut lumen. Gut mucosal immunity regulates tolerance to food and gut contents and is a significant factor in maintaining systemic homeostasis without compromising immunity to pathogens. This is achieved through anatomical structures and signaling pathways that link the tolerogenic potential of the proximal small intestine to systemic immunity. Non-live preparations of microbes isolated from human small intestinal mucosa, and the extracellular vesicles (EVs) which they shed, can resolve systemic inflammation without systemic exposure after oral delivery. The mechanism involves primary interactions with pattern recognition receptors followed by trafficking of immune cells through mesenteric lymph nodes. This generates in the periphery a population of circulating CD4(+) T cells which have regulatory function but an atypical FoxP3(-) phenotype. There is no modification of the resident gut microbiome. Discoveries using this novel approach of targeting mucosal microbial elements to the tolerogenic proximal regions of the small intestine are revealing some of the mysteries of the relationship between the gut and immune system. Frontiers Media S.A. 2022-11-15 /pmc/articles/PMC9706197/ /pubmed/36458009 http://dx.doi.org/10.3389/fimmu.2022.1060607 Text en Copyright © 2022 Bodmer, Itano and McInnes https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Bodmer, Mark
Itano, Andrea
McInnes, Iain
Harnessing the small intestinal axis to resolve systemic inflammation
title Harnessing the small intestinal axis to resolve systemic inflammation
title_full Harnessing the small intestinal axis to resolve systemic inflammation
title_fullStr Harnessing the small intestinal axis to resolve systemic inflammation
title_full_unstemmed Harnessing the small intestinal axis to resolve systemic inflammation
title_short Harnessing the small intestinal axis to resolve systemic inflammation
title_sort harnessing the small intestinal axis to resolve systemic inflammation
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9706197/
https://www.ncbi.nlm.nih.gov/pubmed/36458009
http://dx.doi.org/10.3389/fimmu.2022.1060607
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