Skip to main content
. 2022 Nov 24;16:1002004. doi: 10.3389/fnins.2022.1002004

FIGURE 2.

FIGURE 2

Interactions between the kynurenine pathway and the immune system. A schematic of major leukocyte populations showing the main sites of production and activity of the kynurenine pathway metabolites. The pathway is expressed constitutively in antigen presenting cells (DCs and macrophages) and is regulated by (a) ligation of the CD80/CD86 (B7) complex with CTLA-4 expressed by Treg cells; (b) the glucocorticoid-induced TNF receptor-related protein (GITR) and its ligand GITR-L; (c) the activation of receptors for inflammatory cytokines such as IFN-γ, IL-1β, IL-6, TNF, and with TLRs activated by Pathogen Associated Molecular Patterns (PAMPs, such as LPS, viral dsRNA and mammalian nucleotides) or Damage Associated Molecular Patterns (DAMPS). Activation of the kynurenine pathway generates 3HK, 3HAA, quinolinic acid and kynurenic acid. 3HAA inhibits Th1 cell activity, quinolinic acid is an agonist at glutamate (NMDA) receptors and kynurenic acid is an antagonist at glutamate receptors but can also activate GPR35 protein. NMDA receptors and GPR35 are expressed by many leukocytes and neurons in the CNS. Kynurenine produced by APCs acts as a paracrine agent to enter and influence lymphocytes, activating AHR to promote FoxP3 and Treg differentiation, but suppressing Th17 generation. TLRs, toll-like receptors; 3HAA, 3-hydroxyanthranilic acid; AHR, aryl hydrocarbon receptors.