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Dubosiella newyorkensis modulates immune tolerance in colitis via the L-lysine-activated AhR-IDO1-Kyn pathway
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Dubosiella newyorkensis modulates immune tolerance in colitis via the L-lysine-activated AhR-IDO1-Kyn pathway
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Journal Article
Dubosiella newyorkensis modulates immune tolerance in colitis via the L-lysine-activated AhR-IDO1-Kyn pathway
2024
Overview
Commensal bacteria generate immensely diverse active metabolites to maintain gut homeostasis, however their fundamental role in establishing an immunotolerogenic microenvironment in the intestinal tract remains obscure. Here, we demonstrate that an understudied murine commensal bacterium,
Dubosiella newyorkensis
, and its human homologue
Clostridium innocuum
, have a probiotic immunomodulatory effect on dextran sulfate sodium-induced colitis using conventional, antibiotic-treated and germ-free mouse models. We identify an important role for the
D. newyorkensis
in rebalancing Treg/Th17 responses and ameliorating mucosal barrier injury by producing short-chain fatty acids, especially propionate and L-Lysine (Lys). We further show that Lys induces the immune tolerance ability of dendritic cells (DCs) by enhancing Trp catabolism towards the kynurenine (Kyn) pathway through activation of the metabolic enzyme indoleamine-2,3-dioxygenase 1 (IDO1) in an aryl hydrocarbon receptor (AhR)-dependent manner. This study identifies a previously unrecognized metabolic communication by which Lys-producing commensal bacteria exert their immunoregulatory capacity to establish a Treg-mediated immunosuppressive microenvironment by activating AhR-IDO1-Kyn metabolic circuitry in DCs. This metabolic circuit represents a potential therapeutic target for the treatment of inflammatory bowel diseases.
Here, Zhang
et al
. identify a metabolic axis by which Lys-producing commensal bacterium
Dubosiella newyorkensis
mediates a Treg-mediated immunosuppressive microenvironment by activating AhR-IDO1-Kyn metabolic circuitry in dendritic cells.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
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/ Animals
/ Bacteria
/ Circuits
/ Colitis
/ Colitis - chemically induced
/ Dextran
/ Dextrans
/ Germfree
/ Humanities and Social Sciences
/ Humans
/ Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism
/ Lysine
/ Mice
/ Receptors, Aryl Hydrocarbon - metabolism
/ Science
