Towards Targeting the Aryl Hydrocarbon Receptor in Cystic Fibrosis

Author:

Puccetti Matteo1ORCID,Paolicelli Giuseppe2,Oikonomou Vasileios2ORCID,De Luca Antonella2,Renga Giorgia2,Borghi Monica2,Pariano Marilena2,Stincardini Claudia2,Scaringi Lucia2,Giovagnoli Stefano1ORCID,Ricci Maurizio1,Romani Luigina2,Zelante Teresa2ORCID

Affiliation:

1. Department of Pharmaceutical Sciences, University of Perugia, 06132 Perugia, Italy

2. Department of Experimental Medicine, University of Perugia, 06132 Perugia, Italy

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.

Funder

Specific Targeted Research Project FunMeta

Publisher

Hindawi Limited

Subject

Cell Biology,Immunology

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