Towards Targeting the Aryl Hydrocarbon Receptor in Cystic Fibrosis.

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.

journal_name

Mediators Inflamm

authors

Puccetti M,Paolicelli G,Oikonomou V,De Luca A,Renga G,Borghi M,Pariano M,Stincardini C,Scaringi L,Giovagnoli S,Ricci M,Romani L,Zelante T

doi

10.1155/2018/1601486

subject

Has Abstract

pub_date

2018-02-18 00:00:00

pages

1601486

eissn

0962-9351

issn

1466-1861

journal_volume

2018

pub_type

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