We propose that KYNA, possibly <i>via</i> interaction with aryl hydrocarbon receptor or G-protein-coupled orphan receptor 35, may serve as a counter-regulatory mechanism, decreasing cytotoxicity and inflammation in IBD.
NEW & NOTEWORTHY We report the novel finding that activation of the aryl hydrocarbon receptor with the nontoxic ligand 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) induces regulatory T cells (Tregs) and suppresses inflammatory bowel disease (IBD).
Boosting downstream effects of AHR via UCB or enhancing CD39-mediated ectoenzymatic activity might provide therapeutic options to address development of Th17 dysfunction in IBD.
Ongoing development of therapeutic strategies augmenting CD39 ectonucleotidase bioactivity via cytokines or AHR ligands offers promise for management of thrombophilia, disordered inflammation, and aberrant immune reactivity in IBD.
Reduced production of AHR ligands is also observed in the microbiota from individuals with IBD, particularly in those with CARD9 risk alleles associated with IBD.