1. Amino acid catabolism and altered immune c alls expressing enzymes that catablize amino acids (top) create local conditions where mune cells (bottom) experience reduced access to amino acids triggering effects on ‘TOR and GCB2 pathways that sense levels of amino acids inside cells. Trp depletion and yn production trigger cellular responses via GCN2- and AhR-signaling pathways, ely. to promote regulatory responses by immune cells as indicated fancharged Trp tRNAT? = “*— catabol “ kyn (kyneurenines) Integrated ¥ stress AbR response signaling (ISR) Tolerogenic DCs Treg Treg generation | activation 2. GCN2 and ABR signaling ‘depletion and Kyn production trigger cellular responses via GCN2- and AhR-signalir aways, respectively, to promote regulatory responses by immune cells. See text forareas with reduced Trp ig. 3. Potential physiologic effects of IDO-expressing DCs on Trp levels in lymphoid follicles he model posits how small cohorts of splenic MZ DCs expressing IDO may create region Clow Trp reserves in lymphoid follicles effecting T cells, B cells, and macrophages and ‘Cs inside the follicle to generate immune suppression and tolerance.