Ifngr1-KO Mouse

Ifngr1, encoding interferon gamma receptor 1, is the ligand-binding chain of the interferon-γ receptor. IFN-γ signaling, mediated by the receptor complex of two IFN-γR1 and two IFN-γR2 chains, is crucial for innate immune defense against mycobacterial infections [3]. It is also involved in multiple immune-related pathways, such as those related to T-cell immunity and MHC-I signaling, playing a vital role in the body's immune response. Genetic models, like gene knockout mouse models, are valuable tools to study its function.

In cancer research, loss-of-function experiments have provided insights. For example, loss of optineurin in colorectal cancer leads to immune evasion and immunotherapy resistance via palmitoylation-dependent IFNGR1 lysosomal sorting and degradation. Optineurin deficiency attenuates IFNGR1 and MHC-I expression, impairs T-cell immunity, and reduces immunotherapy efficacy. Pharmacologically targeting IFNGR1 palmitoylation can stabilize IFNGR1, enhance T-cell immunity, and sensitize checkpoint therapy [1]. In macrophages, knockout of RNF149 exacerbates cardiac dysfunction after myocardial infarction. RNF149 restricts inflammation by promoting ubiquitylation-dependent proteasomal degradation of IFNGR1, and loss of IFNGR1 rescues the deleterious effects of RNF149 deficiency on myocardial infarction [2].

In conclusion, Ifngr1 is essential for the body's immune response, especially in defense against mycobacterial infections. Model-based research, particularly gene knockout mouse models, has revealed its significant role in cancer immune evasion and cardiac repair after myocardial infarction. Understanding Ifngr1 function provides potential therapeutic targets for related diseases.

References:

1. Du, Wan, Hua, Fang, Li, Xiong, Fang, Jing-Yuan, Zou, Weiping. 2021. Loss of Optineurin Drives Cancer Immune Evasion via Palmitoylation-Dependent IFNGR1 Lysosomal Sorting and Degradation. In Cancer discovery, 11, 1826-1843. doi:10.1158/2159-8290.CD-20-1571. https://pubmed.ncbi.nlm.nih.gov/33627378/

2. Huang, Chun-Kai, Chen, Zhiyong, Zhou, Zhongxing, Yan, Xiaoxiang, Chai, Dajun. 2024. RNF149 Destabilizes IFNGR1 in Macrophages to Favor Postinfarction Cardiac Repair. In Circulation research, 135, 518-536. doi:10.1161/CIRCRESAHA.123.324023. https://pubmed.ncbi.nlm.nih.gov/38989590/

3. van de Vosse, Esther, van Dissel, Jaap T. 2017. IFN-γR1 defects: Mutation update and description of the IFNGR1 variation database. In Human mutation, 38, 1286-1296. doi:10.1002/humu.23302. https://pubmed.ncbi.nlm.nih.gov/28744922/