Ido1, short for indoleamine 2,3-dioxygenase 1, is a rate-limiting metabolic enzyme. It catalyzes the initial step of the kynurenine (KYN) metabolic pathway, converting tryptophan into formyl-kynurenine. This pathway is involved in de novo NAD+ biosynthesis, 1-carbon metabolism, and generation of kynurenine derivatives. The aryl hydrocarbon receptor (AhR) activation by KYN, a product of the Ido1-catalyzed reaction, leads to the formation of immune-tolerant dendritic cells and regulatory T cells, creating an immunosuppressive environment [1,2,3].

In cancer, Ido1 has been a focus of research. Many preclinical and clinical trials on Ido1 inhibitors have been conducted, as Ido1 over-expression in various human cancers promotes immune tolerance to tumor antigens and tumor neovascularization. However, single-agent Ido1 inhibitors have shown limited efficacy, and combinations with other therapies are being explored [5,4,7,8]. In the context of aging, activation of Ido1-KYN-AhR signaling increases with the aging process, suppressing effector immune cell functions, impairing autophagy, and contributing to age-related diseases [3]. Also, in liver fibrosis, Ido1-mediated M2 macrophage repolarization can be alleviated by certain compounds like corilagin [6].

In conclusion, Ido1 is crucial in regulating immune responses, especially in creating an immunosuppressive microenvironment relevant to cancer and aging. The study of Ido1 in KO/CKO mouse models (not explicitly detailed in the given references but a common approach in gene function studies) could potentially further elucidate its role in these disease conditions, providing more insights for therapeutic strategies.

References:

1. Cheong, Jae Eun, Sun, Lijun. 2017. Targeting the IDO1/TDO2-KYN-AhR Pathway for Cancer Immunotherapy - Challenges and Opportunities. In Trends in pharmacological sciences, 39, 307-325. doi:10.1016/j.tips.2017.11.007. https://pubmed.ncbi.nlm.nih.gov/29254698/

2. Zeitler, Leonie, Murray, Peter J. 2023. IL4i1 and IDO1: Oxidases that control a tryptophan metabolic nexus in cancer. In The Journal of biological chemistry, 299, 104827. doi:10.1016/j.jbc.2023.104827. https://pubmed.ncbi.nlm.nih.gov/37196768/

3. Salminen, Antero. 2022. Role of indoleamine 2,3-dioxygenase 1 (IDO1) and kynurenine pathway in the regulation of the aging process. In Ageing research reviews, 75, 101573. doi:10.1016/j.arr.2022.101573. https://pubmed.ncbi.nlm.nih.gov/35085834/

4. Muller, Alexander J, Mondal, Arpita, Dey, Souvik, Prendergast, George C. 2023. IDO1 and inflammatory neovascularization: bringing new blood to tumor-promoting inflammation. In Frontiers in oncology, 13, 1165298. doi:10.3389/fonc.2023.1165298. https://pubmed.ncbi.nlm.nih.gov/37182174/

5. Li, Fangxuan, Zhang, Rupeng, Li, Shixia, Liu, Juntian. 2017. IDO1: An important immunotherapy target in cancer treatment. In International immunopharmacology, 47, 70-77. doi:10.1016/j.intimp.2017.03.024. https://pubmed.ncbi.nlm.nih.gov/28365507/

6. Wang, Yuhua, Huang, Sha, Kong, Wen, Huang, Shaohui, Lv, Zhiping. 2023. Corilagin alleviates liver fibrosis in zebrafish and mice by repressing IDO1-mediated M2 macrophage repolarization. In Phytomedicine : international journal of phytotherapy and phytopharmacology, 119, 155016. doi:10.1016/j.phymed.2023.155016. https://pubmed.ncbi.nlm.nih.gov/37598639/

7. Zhai, Lijie, Ladomersky, Erik, Lenzen, Alicia, Wu, Meijing, Wainwright, Derek A. 2018. IDO1 in cancer: a Gemini of immune checkpoints. In Cellular & molecular immunology, 15, 447-457. doi:10.1038/cmi.2017.143. https://pubmed.ncbi.nlm.nih.gov/29375124/

8. Wang, Peng-Fei, Yang, Li-Qiang, Shi, Zhao-Hang, Li, Xue-Min, Qiu, Han-Yue. 2022. An updated patent review of IDO1 inhibitors for cancer (2018-2022). In Expert opinion on therapeutic patents, 32, 1145-1159. doi:10.1080/13543776.2022.2151894. https://pubmed.ncbi.nlm.nih.gov/36420761/