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Towards Targeting the Aryl Hydrocarbon Receptor in Cystic Fibrosis

Authors :
Monica Borghi
Maurizio Ricci
Giorgia Renga
Antonella De Luca
Vasileios Oikonomou
Stefano Giovagnoli
Luigina Romani
Claudia Stincardini
Lucia Scaringi
Matteo Puccetti
Teresa Zelante
Marilena Pariano
Giuseppe Paolicelli
Source :
Mediators of Inflammation, Mediators of Inflammation, Vol 2018 (2018)
Publication Year :
2018

Abstract

Tryptophan (trp) metabolism is an important regulatory component of gut mucosal homeostasis and the microbiome. Metabolic pathways targeting the trp can lead to a myriad of metabolites, of both host and microbial origins, some of which act as endogenous low-affinity ligands for the aryl hydrocarbon receptor (AhR), a cytosolic, ligand-operated transcription factor that is involved in many biological processes, including development, cellular differentiation and proliferation, xenobiotic metabolism, and the immune response. Low-level activation of AhR by endogenous ligands is beneficial in the maintenance of immune health and intestinal homeostasis. We have defined a functional node whereby certain bacteria species contribute to host/microbial symbiosis and mucosal homeostasis. A microbial trp metabolic pathway leading to the production of indole-3-aldehyde (3-IAld) by lactobacilli provided epithelial protection while inducing antifungal resistance via the AhR/IL-22 axis. In this review, we highlight the role of AhR in inflammatory lung diseases and discuss the possible therapeutic use of AhR ligands in cystic fibrosis.

Details

Language :
English
Database :
OpenAIRE
Journal :
Mediators of Inflammation, Mediators of Inflammation, Vol 2018 (2018)
Accession number :
edsair.doi.dedup.....d4c03d399d59c16356bf7bea6dc0dfbd