Publication details

A microbially produced AhR ligand promotes a Tph1-driven tolerogenic program in multiple sclerosis

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Authors

ZELANTE Teresa PAOLICELLI Giuseppe FALLARINO Francesca GARGARO Marco VASCELLI Gianluca MARCO De Zuani FRIČ Jan LÁZNIČKOVÁ Petra HORTOVÁ KOHOUTKOVÁ Marcela MACCHIARULO Antonio DOLCIAMI Daniela PIERACCINI Giuseppe GAETANI Lorenzo SCALISI Giulia TREVISAN Caterina FROSSI Barbara PUCILLO Carlo ANTONELLA De Luca NUNZI Emilia SPACCAPELO Roberta PARIANO Marilena BORGHI Monica BOSCARO Francesca ROMOLI Riccardo MANCINI Andrea GENTILI Lucia RENGA Giorgia COSTANTINI Claudio PUCCETTI Matteo GIOVAGNOLI Stefano RICCI Maurizio ANTONINI Martina CALABRESI Paolo PUCCETTI Paolo MASSIMILIANO Di Filippo ROMANI Luigina

Year of publication 2024
Type Article in Periodical
Magazine / Source Scientific Reports
MU Faculty or unit

Faculty of Medicine

Citation
Web https://www.nature.com/articles/s41598-024-57400-8
Doi http://dx.doi.org/10.1038/s41598-024-57400-8
Keywords Mast cells; Aryl hydrocarbon receptor; Serotonin; 3-IAld; Multiple sclerosis
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Description 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.
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