Research Article: Gut bacterial lauroyl tryptamine reduces GPR183-associated inflammatory responses in human macrophages and T cells in vitro
Abstract:
Recent research has highlighted the role of gut microbiota in producing bioactive metabolites that interact with G-protein coupled receptors (GPRs) and influence immune responses. Lauroyl tryptamine (LT), a metabolite produced by Agathobacter rectalis (formerly Eubacterium rectale ), has been reported to antagonize GPR183, a receptor implicated in inflammatory bowel diseases (IBD). LT inhibits the binding of GPR183 with its natural ligands 7a,25-dihydroxycholesterol (OHC).
Here, we analyzed the GPR183 gene expression in intestinal tissues from IBD patients and non-IBD controls, as well as our previous single-cell transcriptomic dataset to identify key GPR183-expressing cells. We then use in vitro THP-1 derived macrophage and Jurkat T cell culture to test the effects of LT on inflammatory responses.
The GPR183 gene expression is elevated specifically in colonic and rectal tissues of ulcerative colitis patients, but not in Crohn’s disease or ileal tissue. By analyzing single-cell transcriptomic dataset, we identified monocytes/macrophages, T cells, B cells, and innate lymphoid cells as key GPR183 -expressing populations in human intestine. Using cell culture models, we demonstrated that LT modulates inflammatory pathways. In LPS-stimulated macrophages, OHC increased transcription of pro-inflammatory genes IL6, TNFA , and IL1B , which are reduced by LT. In activated Jurkat T cells, LT slightly decreased the OHC-mediated increase in the transcription of IL2. These findings support the hypothesis that LT, a known GPR183 antagonist, could modulate GPR183-associated inflammation in human macrophages and T cells in a context- and cell type-dependent manner, offering potential mechanistic insights into bioactive metabolite-mediated host-microbiota interactions in human intestine.
Introduction:
Recent research has highlighted the role of gut microbiota in producing bioactive metabolites that interact with G-protein coupled receptors (GPRs) and influence immune responses. Lauroyl tryptamine (LT), a metabolite produced by Agathobacter rectalis (formerly Eubacterium rectale ), has been reported to antagonize GPR183, a receptor implicated in inflammatory bowel diseases (IBD). LT inhibits the binding of GPR183 with its natural ligands 7a,25-dihydroxycholesterol (OHC).
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