Figure 2.

Simplified scheme of IDO activity in immune regulation. IDO is expressed in various cells, such as APCs, fibroblasts, endothelial, epithelial, smooth muscle cells, etc., in response to proinflammatory mediators. Due to IDO activity, decreased levels of tryptophan activate the GCN2 kinase, which leads to T-cell anergy, T-cell cycle arrest and apoptosis. The deactivated mTOR pathway results in suppressed T-cell proliferation and differentiation. Increased levels of toxic tryptophan-kynurenine pathway metabolites induce effector T-cell apoptosis and promote Treg formation and activation. Abbreviations: Trp: tryptophan, IDO: indoleamine-2,3-dioxygenase, APCs: antigen-presenting cells, GCN2: general control nonderepressible 2, mTOR: mammalian target of rapamycin and Tregs–regulatory T cells.