Ido2, indoleamine 2,3-dioxygenase 2, is an initial and rate-limiting enzyme of the kynurenine pathway of tryptophan catabolism [1]. It is an immunomodulatory molecule with potential effects on various diseases such as cancer and autoimmunity [2]. Ido2 and Ido1 originated from gene duplication before vertebrate divergence, but Ido2 has much lower catalytic activity toward tryptophan [4].

In mouse models, Ido2 gene deletion does not affect embryonic development or hematopoiesis, but leads to defects in allergic or autoimmune responses and in the ability of Ido1 to influence the generation of T regulatory cells [3]. In the KRN transgenic mouse model of rheumatoid arthritis, Ido2 deletion selectively blunts responses to autoantigen [3]. Also, catalytically inactive Ido2 knock-in mice show attenuated contact hypersensitivity, while induction of autoimmune arthritis is unaffected by the absence of Ido2 enzymatic activity [5].

In conclusion, Ido2 plays a role in immunomodulation and is involved in the pathogenesis of autoimmune diseases and cancer. Mouse models, especially gene knockout and knock-in models, have been crucial in revealing its non-enzymatic and enzymatic functions in these disease conditions, helping to understand its role in the immune response and providing potential therapeutic targets for related diseases.

References:

1. Li, Pengcheng, Xu, Weiqi, Liu, Furong, Liang, Huifang, Song, Jia. 2021. The emerging roles of IDO2 in cancer and its potential as a therapeutic target. In Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 137, 111295. doi:10.1016/j.biopha.2021.111295. https://pubmed.ncbi.nlm.nih.gov/33550042/

2. Merlo, Lauren M F, Mandik-Nayak, Laura. 2016. IDO2: A Pathogenic Mediator of Inflammatory Autoimmunity. In Clinical medicine insights. Pathology, 9, 21-28. doi:. https://pubmed.ncbi.nlm.nih.gov/27891058/

3. Prendergast, George C, Metz, Richard, Muller, Alexander J, Merlo, Lauren M F, Mandik-Nayak, Laura. 2014. IDO2 in Immunomodulation and Autoimmune Disease. In Frontiers in immunology, 5, 585. doi:10.3389/fimmu.2014.00585. https://pubmed.ncbi.nlm.nih.gov/25477879/

4. Suvieri, Chiara, Belladonna, Maria Laura, Volpi, Claudia. 2024. The Two Sides of Indoleamine 2,3-Dioxygenase 2 (IDO2). In Cells, 13, . doi:10.3390/cells13221894. https://pubmed.ncbi.nlm.nih.gov/39594642/

5. Merlo, Lauren M F, Peng, Weidan, DuHadaway, James B, Muller, Alexander J, Mandik-Nayak, Laura. 2021. The Immunomodulatory Enzyme IDO2 Mediates Autoimmune Arthritis through a Nonenzymatic Mechanism. In Journal of immunology (Baltimore, Md. : 1950), 208, 571-581. doi:10.4049/jimmunol.2100705. https://pubmed.ncbi.nlm.nih.gov/34965962/