3,4-DAA, an orally active synthetic tryptophan catabolite, treats established autoimmune neuroinflammation

Depletion of the essential amino acid tryptophan (Trp) by antigen-presenting cells (APCs) is believed to suppress antigen-specific T cell responses. For instance, inhibition of indoleamine-2,3-dioxygenase (IDO) which is the rate-limiting enzyme in Trp catabolism induces the rejection of tumors and fetal allografts. Thus, IDO appears to play a central role in maintaining T cell tolerance. Using gene microarray analyses we show that IDO transcripts were more abundant in myelin-specific T cells stimulated with tolerogenic altered self-peptide compared to myelin-specific T cells stimulated with native self-peptide.…