Acute exercise increases systemic kynurenine pathway metabolites and activates the AHR in human PBMCs

The kynurenine pathway of tryptophan degradation generates several metabolites such as kynurenine or kynurenic acid that serve as endogenous ligands of the aryl hydrocarbon receptor (AHR). Due to its distinct biological roles particularly modulating the immune system, the AHR is a current therapeutic target across different inflammation-related diseases. Here, we show an exercise-induced increase in AHR ligand availability on a systemic level and a kynurenine pathway activation in peripheral mononuclear blood cells (PBMCs). Concurrently, the AHR is activated in PBMCs following acute exercise, with effects being dependent on exercise intensity. In conclusion, these data indicate a novel mechanistic link how exercise modulates the immune system through the kynurenine pathway-AHR axis, potentially underlying exercise-induced benefits in various chronic diseases.