A microbially produced AhR ligand promotes a Tph1-driven tolerogenic program in multiple sclerosis
Year: 2024
Type: article
Abstract: Multiple sclerosis is a debilitating autoimmune disease, characterized by chronic inflammation of the central nervous system. While the significance of the gut microbiome on multiple sclerosis pathogenesis is established, the underlining mechanisms are unknown. We found that serum levels of the microbial postbiotic tryptophan metabolite indole-3-carboxaldehyde (3-IAld) inversely correlated with disease duration in multiple sclerosis patients. Much like the host-derived tryptophan derivative L-Kynurenine, 3-IAld would bind and activate the Aryl hydrocarbon Receptor (AhR), which, in turn, controls endogenous tryptophan catabolic pathways. As a result, in peripheral lymph nodes, microbial 3-IAld, affected mast-cell tryptophan metabolism, forcing mast cells to produce serotonin via Tph1. We thus propose a protective role for AhR-mast-cell activation driven by the microbiome, whereby natural metabolites or postbiotics will have a physiological role in immune homeostasis and may act as therapeutic targets in autoimmune diseases.
Source: Scientific Reports
Authors: Teresa Zelante, Giuseppe Paolicelli, Francesca Fallarino, Marco Gargaro, Gianluca Vascelli, Marco De Zuani, Jan Fric, Petra Laznickova, Marcela Hortova Kohoutkova, Antonio Macchiarulo, Daniela Dolciami, Giuseppe Pieraccini, Lorenzo Gaetani, Giulia Scalisi, Caterina Trevisan, Barbara Frossi, Carlo Pucillo, Antonella De Luca, Emilia Nunzi, Roberta Spaccapelo, Marilena Pariano, Monica Borghi, Francesca Boscaro, Riccardo Romoli, Andrea Mancini, Lucia Gentili, Giorgia Renga, Claudio Costantini, Matteo Puccetti, Stefano Giovagnoli, Maurizio Ricci, Martina Antonini, Paolo Calabresi, Paolo Puccetti, Massimiliano Di Filippo, Luigina Romani
Institutions: University of Perugia, Consorzio Interuniversitario per le Biotecnologie, International Clinical Research Center, St. Anne's University Hospital Brno, St. Anne's University Hospital Brno, Masaryk University, Institute of Haematology and Blood Transfusion, University of Florence, University of Udine, Agostino Gemelli University Polyclinic, Istituti di Ricovero e Cura a Carattere Scientifico
Language: English
Subfield: Biological Psychiatry
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,590
Funders: Fondazione Italiana Sclerosi Multipla, European Commission, Ministerstvo Školství, Mládeže a Tělovýchovy, Ministerstvo Zdravotnictví Ceské Republiky, Fondazione Cassa di Risparmio di Perugia, Associazione Italiana per la Ricerca sul Cancro, Università degli Studi di Perugia, NextGenerationEU
OpenAlex ID: W4393011002