Scientific Reports (Mar 2024)
A microbially produced AhR ligand promotes a Tph1-driven tolerogenic program in multiple sclerosis
- 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
Affiliations
- Teresa Zelante
- Department of Medicine and Surgery, University of Perugia
- Giuseppe Paolicelli
- Department of Medicine and Surgery, University of Perugia
- Francesca Fallarino
- Department of Medicine and Surgery, University of Perugia
- Marco Gargaro
- Department of Medicine and Surgery, University of Perugia
- Gianluca Vascelli
- Department of Medicine and Surgery, University of Perugia
- Marco De Zuani
- International Clinical Research Centre, St. Anne’s University Hospital Brno
- Jan Fric
- International Clinical Research Centre, St. Anne’s University Hospital Brno
- Petra Laznickova
- International Clinical Research Centre, St. Anne’s University Hospital Brno
- Marcela Hortova Kohoutkova
- International Clinical Research Centre, St. Anne’s University Hospital Brno
- Antonio Macchiarulo
- Department of Pharmaceutical Science, University of Perugia
- Daniela Dolciami
- Department of Pharmaceutical Science, University of Perugia
- Giuseppe Pieraccini
- Mass Spectrometry Center (CISM), University of Florence
- Lorenzo Gaetani
- Department of Medicine and Surgery, University of Perugia
- Giulia Scalisi
- Department of Medicine and Surgery, University of Perugia
- Caterina Trevisan
- Department of Medical and Biological Science, University of Udine
- Barbara Frossi
- Department of Medical and Biological Science, University of Udine
- Carlo Pucillo
- Department of Medical and Biological Science, University of Udine
- Antonella De Luca
- Department of Medicine and Surgery, University of Perugia
- Emilia Nunzi
- Department of Medicine and Surgery, University of Perugia
- Roberta Spaccapelo
- Department of Medicine and Surgery, University of Perugia
- Marilena Pariano
- Department of Medicine and Surgery, University of Perugia
- Monica Borghi
- Department of Medicine and Surgery, University of Perugia
- Francesca Boscaro
- Mass Spectrometry Center (CISM), University of Florence
- Riccardo Romoli
- Mass Spectrometry Center (CISM), University of Florence
- Andrea Mancini
- Department of Medicine and Surgery, University of Perugia
- Lucia Gentili
- Department of Medicine and Surgery, University of Perugia
- Giorgia Renga
- Department of Medicine and Surgery, University of Perugia
- Claudio Costantini
- Department of Medicine and Surgery, University of Perugia
- Matteo Puccetti
- Department of Pharmaceutical Science, University of Perugia
- Stefano Giovagnoli
- Department of Pharmaceutical Science, University of Perugia
- Maurizio Ricci
- Department of Pharmaceutical Science, University of Perugia
- Martina Antonini
- Department of Medicine and Surgery, University of Perugia
- Paolo Calabresi
- Unità di Neurologia, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS
- Paolo Puccetti
- Department of Medicine and Surgery, University of Perugia
- Massimiliano Di Filippo
- Department of Medicine and Surgery, University of Perugia
- Luigina Romani
- Department of Medicine and Surgery, University of Perugia
- DOI
- https://doi.org/10.1038/s41598-024-57400-8
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 16
Abstract
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.
Keywords
