IDO1 induction and proinflammatory cytokines. IFN-γ drives intense enzymatic IDO1 activity, resulting in TRP depletion and high-level production of immunoregulatory TRP metabolites, KYNs, which may foster Tregs expansion. Induced Tregs use TGF-β to maintain an IDO1-dependent regulatory environment, with IDO1 mostly functioning as a signaling molecule. Both mechanisms are interrupted by IL-6, which drives IDO1 degradation as potent inflammatory stimuli enter the local environment [85].