ITIM-regulated expression of IDO. TGF-β and IL-6 regulate IDO expression in a positive and negative fashion, respectively. TGF-β promotes anchoring of SHP-1/2 to phosphorylated IDO ITIMs, initiating a molecular pathway that culminates in de novo synthesis of IDO and amplified tryptophan (TRP) conversion into kynurenine (KYN). This TGF-β-induced mechanism contributes to the maintenance and spreading of immune tolerance (INFECTIOUS TOLERANCE). IL-6 induces SOCS3 and favors its association with IDO, targeting the enzyme for proteasomal degradation. This mechanism, by affecting IDO lifespan, subverts the tolerogenic program of the DC, promoting immune activation (IMMUNITY).