IDO2

IDO2 (indoleamine 2,3-dioxygenase 2) is a heme-containing enzyme involved in the initial and rate-limiting step of tryptophan catabolism through the kynurenine pathway, linking amino acid metabolism to immune regulation^[1][2]. Mechanistically, IDO2 contributes to immunomodulatory processes associated with kynurenine pathway activity and has been implicated in the regulation of adaptive immune responses and immune tolerance^[2][3]. In disease models, IDO2 has been associated with inflammatory and autoimmune phenotypes, where genetic deletion or functional inhibition alters autoantigen-driven immune responses, particularly in models of rheumatoid arthritis and inflammatory autoimmunity^[2][4]. Compared with the closely related isoform IDO1, IDO2 displays a more restricted expression pattern, being detected primarily in antigen-presenting cells, liver, kidney, brain, and placenta, and exhibits distinct enzymatic and immunological functions rather than serving as a redundant paralog^[2][5]. Experimental evidence further indicates that IDO2 can regulate inflammatory responses through mechanisms involving B-cell-mediated immune activation and T-cell help, distinguishing its role from the broadly immunosuppressive activities commonly attributed to IDO1^[4][5]. For research applications, D-1-methyl-tryptophan (D-1MT, indoximod) was identified as a preferred biochemical inhibitor of IDO2, and the development of selective IDO2 inhibitors has enabled more precise investigation of IDO2-dependent pathways in autoimmunity, immune tolerance, and cancer-associated immune regulation^[6][7].

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