Figure 10.

Scheme showing how tryptophan plays a role in the development of type 1 diabetes mellitus (type 1 DM) and type 2 DM. Tryptophan is an essential amino acid. Gut bacteria convert tryptophan into indole derivatives: indol-3-acetic acid, indoxyl-3-sulfate, indole-3-propionic acid, and indole-3-aldehyde that are ligands for the aryl hydrocarbon receptor (AHR). Tryptophan indole derivatives activate AHR in gut-resident T cells and innate lymphoid cells that produce IL-22, which protects against inflammation. Tryptophan metabolites by signaling through AHR influence a type 1 IFN signaling pathway that reduces NF-κB-driven inflammation (via SOCS2) and inhibits/ameliorates autoimmunity. Thus, tryptophan and its indole metabolites may have a role in autoimmune diseases (AID), such as type 1 DM and central nervous system AID. Tryptophan is also the precursor of serotonin that has immunomodulatory and cytoprotective actions (see Figure 9) and enhances lipoxin A4 production (unpublished data) and possibly that of resolvins, protectins, and maresins; anti-inflammatory bioactive lipids, which prevent type 1 DM (see Figure 8).