Fig. 2.

The main physiological activity of PIC in the human CNS. PIC is a terminal metabolite of L-tryptophan metabolism via the kynurenine pathway. The exact role of PIC is not known, but it has been reported to be involved in neuroprotective, immunological, and anti-proliferative functions. PIC acts as an iron chelator, causing iron to be unavailable for normal cell development. PIC also limits presynaptic glutamate release from nerve terminals, selectively modulating QUIN excitotoxicity, which depends on glutamate input. PIC has a dose-dependent negative regulatory function on CD4⁺ T-cell proliferation and the ability to generate profound anergy and suppress CD4⁺ T-cell polarization. IDO competent DCs generate an immunosuppressive milieu that converts local T-cell activity from immunogenic to tolerogenic. DCs expressing IDO secrete immunosuppressive cytokines that in turn block effector CD8⁺ T cells while inducing Tregs. IDO indoleamine 2, 3-dioxygenase, PIC picolinic acid, DCs dendritic cells, CNS central nervous system, QUIN quinolinic acid, Tregs regulatory T cells