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cGAS-STING signaling pathway in intestinal homeostasis and diseases

The intestinal mucosa is constantly exposed to commensal microbes, opportunistic pathogens, toxins, luminal components and other environmental stimuli. The intestinal mucosa consists of multiple differentiated cellular and extracellular components that form a critical barrier, but is also equipped f...

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Autores principales: Yang, Yuchen, Wang, Li, Peugnet-González, Ivonne, Parada-Venegas, Daniela, Dijkstra, Gerard, Faber, Klaas Nico
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10538549/
https://www.ncbi.nlm.nih.gov/pubmed/37781354
http://dx.doi.org/10.3389/fimmu.2023.1239142
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author Yang, Yuchen
Wang, Li
Peugnet-González, Ivonne
Parada-Venegas, Daniela
Dijkstra, Gerard
Faber, Klaas Nico
author_facet Yang, Yuchen
Wang, Li
Peugnet-González, Ivonne
Parada-Venegas, Daniela
Dijkstra, Gerard
Faber, Klaas Nico
author_sort Yang, Yuchen
collection PubMed
description The intestinal mucosa is constantly exposed to commensal microbes, opportunistic pathogens, toxins, luminal components and other environmental stimuli. The intestinal mucosa consists of multiple differentiated cellular and extracellular components that form a critical barrier, but is also equipped for efficient absorption of nutrients. Combination of genetic susceptibility and environmental factors are known as critical components involved in the pathogenesis of intestinal diseases. The innate immune system plays a critical role in the recognition and elimination of potential threats by detecting pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). This host defense is facilitated by pattern recognition receptors (PRRs), in which the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway has gained attention due to its role in sensing host and foreign double-stranded DNA (dsDNA) as well as cyclic dinucleotides (CDNs) produced by bacteria. Upon binding with dsDNA, cGAS converts ATP and GTP to cyclic GMP-AMP (cGAMP), which binds to STING and activates TANK binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3), inducing type I interferon (IFN) and nuclear factor kappa B (NF-κB)-mediated pro-inflammatory cytokines, which have diverse effects on innate and adaptive immune cells and intestinal epithelial cells (IECs). However, opposite perspectives exist regarding the role of the cGAS-STING pathway in different intestinal diseases. Activation of cGAS-STING signaling is associated with worse clinical outcomes in inflammation-associated diseases, while it also plays a critical role in protection against tumorigenesis and certain infections. Therefore, understanding the context-dependent mechanisms of the cGAS-STING pathway in the physiopathology of the intestinal mucosa is crucial for developing therapeutic strategies targeting the cGAS-STING pathway. This review aims to provide insight into recent findings of the protective and detrimental roles of the cGAS-STING pathway in intestinal diseases.
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spelling pubmed-105385492023-09-29 cGAS-STING signaling pathway in intestinal homeostasis and diseases Yang, Yuchen Wang, Li Peugnet-González, Ivonne Parada-Venegas, Daniela Dijkstra, Gerard Faber, Klaas Nico Front Immunol Immunology The intestinal mucosa is constantly exposed to commensal microbes, opportunistic pathogens, toxins, luminal components and other environmental stimuli. The intestinal mucosa consists of multiple differentiated cellular and extracellular components that form a critical barrier, but is also equipped for efficient absorption of nutrients. Combination of genetic susceptibility and environmental factors are known as critical components involved in the pathogenesis of intestinal diseases. The innate immune system plays a critical role in the recognition and elimination of potential threats by detecting pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). This host defense is facilitated by pattern recognition receptors (PRRs), in which the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway has gained attention due to its role in sensing host and foreign double-stranded DNA (dsDNA) as well as cyclic dinucleotides (CDNs) produced by bacteria. Upon binding with dsDNA, cGAS converts ATP and GTP to cyclic GMP-AMP (cGAMP), which binds to STING and activates TANK binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3), inducing type I interferon (IFN) and nuclear factor kappa B (NF-κB)-mediated pro-inflammatory cytokines, which have diverse effects on innate and adaptive immune cells and intestinal epithelial cells (IECs). However, opposite perspectives exist regarding the role of the cGAS-STING pathway in different intestinal diseases. Activation of cGAS-STING signaling is associated with worse clinical outcomes in inflammation-associated diseases, while it also plays a critical role in protection against tumorigenesis and certain infections. Therefore, understanding the context-dependent mechanisms of the cGAS-STING pathway in the physiopathology of the intestinal mucosa is crucial for developing therapeutic strategies targeting the cGAS-STING pathway. This review aims to provide insight into recent findings of the protective and detrimental roles of the cGAS-STING pathway in intestinal diseases. Frontiers Media S.A. 2023-09-14 /pmc/articles/PMC10538549/ /pubmed/37781354 http://dx.doi.org/10.3389/fimmu.2023.1239142 Text en Copyright © 2023 Yang, Wang, Peugnet-González, Parada-Venegas, Dijkstra and Faber 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
Yang, Yuchen
Wang, Li
Peugnet-González, Ivonne
Parada-Venegas, Daniela
Dijkstra, Gerard
Faber, Klaas Nico
cGAS-STING signaling pathway in intestinal homeostasis and diseases
title cGAS-STING signaling pathway in intestinal homeostasis and diseases
title_full cGAS-STING signaling pathway in intestinal homeostasis and diseases
title_fullStr cGAS-STING signaling pathway in intestinal homeostasis and diseases
title_full_unstemmed cGAS-STING signaling pathway in intestinal homeostasis and diseases
title_short cGAS-STING signaling pathway in intestinal homeostasis and diseases
title_sort cgas-sting signaling pathway in intestinal homeostasis and diseases
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10538549/
https://www.ncbi.nlm.nih.gov/pubmed/37781354
http://dx.doi.org/10.3389/fimmu.2023.1239142
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