Microbiota-Derived Metabolites Suppress Arthritis by Amplifying Aryl-Hydrocarbon Receptor Activation in Regulatory B Cells

Rosser, Elizabeth C.; Piper, Christopher; Matei, Diana E.; Blair, Paul A.; Rendeiro, André F.; Orford, Michael; Alber, Dagmar; Krausgruber, Thomas; Catalán, Diego; Klein, Nigel; Manson, Jessica; Drozdov, Ignat; Bock, Christoph; Wedderburn, Lucy R.; Eaton, Simon; Mauri, Claudia

doi:10.1016/j.cmet.2020.03.003

articleCell MetabolismMar 25, 2020HYBRID OA

Microbiota-Derived Metabolites Suppress Arthritis by Amplifying Aryl-Hydrocarbon Receptor Activation in Regulatory B Cells

ECElizabeth C. Rosser CPChristopher Piper DEDiana E. Matei PAPaul A. Blair AFAndré F. Rendeiro

Great Ormond Street Hospital · Arthritis UK · +9 more institutions

PubMed

Indexed incrossrefpubmed

Abstract

The differentiation of IL-10-producing regulatory B cells (Bregs) in response to gut-microbiota-derived signals supports the maintenance of tolerance. However, whether microbiota-derived metabolites can modulate Breg suppressive function remains unknown. Here, we demonstrate that rheumatoid arthritis (RA) patients and arthritic mice have a reduction in microbial-derived short-chain fatty acids (SCFAs) compared to healthy controls and that in mice, supplementation with the SCFA butyrate reduces arthritis severity. Butyrate supplementation suppresses arthritis in a Breg-dependent manner by increasing the level of the serotonin-derived metabolite 5-Hydroxyindole-3-acetic acid (5-HIAA), which activates the…

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Topics & keywords

Topics

Keywords

Butyrate
Aryl hydrocarbon receptor
Metabolite
Arthritis
Gut flora
Rheumatoid arthritis
Immunology
Biology

UN Sustainable Development Goals

Good health and well-being

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