Endogenous Indole Pyruvate Pathway for Tryptophan Metabolism Mediated by IL4I1

Abstract

L-tryptophan (Trp) is widely used in food and feed enforcement to play an important role in biological processes. Various metabolites of Trp perform its potent function. The indole pyruvate pathway is one of the main pathways of Trp metabolism in the gut microbiota, providing numerous indole-derivatives, which can modulate intestinal homeostasis and mucosal immunity by activating the aryl hydrocarbon receptor (AHR) signaling pathway. In this study, we constructed an IL4I1-overexpressed 293T cell line and found that IL4I1 can catalyze Trp to produce indole-3-acetic acid (IAA) and indole-3-carboxaldehyde (IAld). Moreover, both IAA and IAld are accumulated in dendritic cells (DCs) and can stimulate the expression of CYP1A1. Our results demonstrate the existence of the indole pyruvate pathway in host cells with IL4I1 as the key enzyme. The IL4I1-mediated Trp metabolism implies the role of dietary impact on immunity.

Production of Hydroxycarboxylic Acid Receptor 3 (HCA3) Ligands by Bifidobacterium

“…Aryl-pyr-As are the intermediate metabolites of aryl-LAs [13]. Aryl-pyr-As have been reported as endogenous metabolite mediators in the host, such as AhR ligands [26,27]. Using our assay system, we confirmed the ligand activity of IpyA against AhR (Figure 3H).…”

Control of T-Cell Activation and Signaling by Amino-Acid Catabolizing Enzymes

“…This effect appears to involve diminution of mTORC1 signaling (Cousin et al, 2015). However, it has also been recently observed that IL4I1 degradation of tryptophan [a minor substrate in comparison to phenylalanine (Boulland et al, 2007)] produces indole derivatives that can activate the AHR pathway (Sadik et al, 2020;Zhang et al, 2020). Finally, IL4I1 modulates the priming of CD8 + T cells.…”

An Insight into the Roles of Dietary Tryptophan and Its Metabolites in Intestinal Inflammation and Inflammatory Bowel Disease

“…Fortunately, microbiota-mediated Trp metabolites serve as a reliable source of AhR ligands and influence the activity of AhR. Some intestinal symbiotic bacteria can metabolize Trp and produce numerous metabolites, such as indole, tryptamine, and indole derivatives IAAId, IAA, IAId, and IPA, which have been proved to exhibit species selective preference upon combining with AhR and firmly elucidate the activation of AhR, [74,78,79,95] and thus are involved in regulating immune response and affecting intestinal function. For example, IAId with AhR activation release IL-22 that could guarantee mucosal defense mechanisms and intestinal homeostasis.…”