| IDO |
role in immunoregulation during infection, autoimmunity, pregnancy, transplantation and neoplasia |
|
IDO activation [70,89] |
Elevated levels of kynurenine metabolites, among others QUIN with its neurotoxic and ROS-generating properties TRP depletion decreased production of serotonin Antimicrobial effects (TRP depletion, potentiation of polymorphonuclear cell function) Immunotolerance via TRP depletion in the microenvironment—with suppression of antigen-specific T-cells and/or preferential apoptosis of helper T lymphocytes (by some KYN-downstream products) The generation of forkhead box P3-positive (FOXP3) regulatory T cells (Treg)—inhibition of both Th1 and Th2 cell response to regain balance The enhancement of TGFβ-mediated T cell differentiation (Treg); the shift of dendritic cells to become tolerogenic Immunosuppression during pregnancy The inhibition of Th1 cell responses and selective support of Th2 actions |
| L-KYN/KYNA |
blockage of antigens-driven specific T-cell proliferation,
induction of T-cell death
the reduction of IL-4 release (inducer of Th2 type reaction) from iNKT (invariant natural killer T cell) cells via GPR35 activation [90]
the inhibition of LPS-induced TNF-α secretion in peripheral blood mononuclear cells via GPR35 receptor activation [72]; and also on CD14+ peripheral blood monocytes [57,91]);
the attenuation of the proinflammatory cytokine HMGB1 (high-mobility group box protein 1) of peripheral blood monocytes and of the release of defensin-α (also known a as HNP1-3 being an immunomodulatory peptide, taking part in microbial killing) from neutrophils [91]; the suppression of and proapoptotic action on natural killer cells (NK) (which also play a role in the immunosurveillance of cancer cells) |
| 3-OH-AA and QUIN |
the selective apoptosis of Th1 helper cells, promoting the proliferation of Th2 cells |
| QUIN |
increase in MCP-1 expression (a strong chemoattractant for monocytes in the brain). |
