| Citation |
ZELANTE, Teresa, Giuseppe PAOLICELLI, Francesca FALLARINO,
Marco GARGARO, Gianluca VASCELLI, De Zuani MARCO, Jan FRIČ,
Petra LÁZNIČKOVÁ, Marcela HORTOVÁ KOHOUTKOVÁ, Antonio
MACCHIARULO, Daniela DOLCIAMI, Giuseppe PIERACCINI, Lorenzo
GAETANI, Giulia SCALISI, Caterina TREVISAN, Barbara FROSSI,
Carlo PUCILLO, De Luca ANTONELLA, 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, Di Filippo MASSIMILIANO and Luigina ROMANI. A
microbially produced AhR ligand promotes a Tph1-driven
tolerogenic program in multiple sclerosis. Scientific Reports.
Berlin: NATURE RESEARCH, 2024, vol. 14, No 1, p. 1-16. ISSN
2045-2322. Available from:
https://dx.doi.org/10.1038/s41598-024-57400-8. |
| 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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