Ifnar2-KO Mouse

Ifnar2, also known as interferon alpha and beta receptor subunit 2, is a key component of the type I interferon receptor (IFNAR) heterodimer, along with Ifnar1. Type I interferons are cytokines with antiviral, antiproliferative, antiangiogenic, and immunomodulatory activities, and Ifnar2 is essential for their signaling pathway. This signaling is crucial for innate and adaptive immune responses against viruses and other pathogens [2].

In mouse models of type 1 diabetes (T1D), IFNAR2 mRNA and protein expression levels were significantly higher in T1D mice compared to controls. Knockdown of IFNAR2 in T1D mice reduced the inflammatory response and improved islet function, as indicated by changes in blood glucose, cytokine levels, and the number of dendritic cells [1]. In anti-influenza immunity, Ifnar2 -/- mice displayed increased and accelerated morbidity and mortality compared to wild-type mice upon influenza A virus (IAV) infection, highlighting its critical role in antiviral immunity. Additionally, Ifnar2 -/- mice showed different susceptibilities to post-influenza bacterial superinfections compared to Ifnar1 -/- mice, indicating distinct roles of the two receptor subunits [3]. In human macrophages and microglia, IFNAR2 deficiency led to significantly enhanced Zika virus replication and cell death, revealing the inherent cytopathicity of the virus towards these cells and the importance of IFN-I signaling via IFNAR2 in maintaining a non-cytolytic state of viral replication [4].

In conclusion, Ifnar2 is vital for type I interferon signaling, playing a significant role in immune responses against various viral infections such as influenza and Zika virus. In disease conditions like T1D, it is involved in the inflammatory response and islet function. Studies using gene knockout mouse models have been instrumental in revealing these functions of Ifnar2, providing insights into the underlying mechanisms of immune responses and disease pathogenesis.

References:

1. Sun, Wei, Liu, Jing, Zhao, Renhao, Zhang, Tongyu, Wang, Guofeng. 2022. Knockdown of IFNAR2 reduces the inflammatory response in mouse model of type 1 diabetes. In Biochemical and biophysical research communications, 619, 9-14. doi:10.1016/j.bbrc.2022.06.028. https://pubmed.ncbi.nlm.nih.gov/35728283/

2. Walter, Mark R. 2020. The Role of Structure in the Biology of Interferon Signaling. In Frontiers in immunology, 11, 606489. doi:10.3389/fimmu.2020.606489. https://pubmed.ncbi.nlm.nih.gov/33281831/

3. Shepardson, Kelly M, Larson, Kyle, Johns, Laura L, Henderson, Haley, Rynda-Apple, Agnieszka. 2018. IFNAR2 Is Required for Anti-influenza Immunity and Alters Susceptibility to Post-influenza Bacterial Superinfections. In Frontiers in immunology, 9, 2589. doi:10.3389/fimmu.2018.02589. https://pubmed.ncbi.nlm.nih.gov/30473701/

4. Hanrath, Aidan T, Hatton, Catherine F, Gothe, Florian, Hambleton, Sophie, Duncan, Christopher J A. 2022. Type I interferon receptor (IFNAR2) deficiency reveals Zika virus cytopathicity in human macrophages and microglia. In Frontiers in immunology, 13, 1035532. doi:10.3389/fimmu.2022.1035532. https://pubmed.ncbi.nlm.nih.gov/36439115/