Ifnar2, or interferon alpha and beta receptor subunit 2, is a crucial component of the type I interferon receptor (IFNAR) complex, along with Ifnar1. Type I interferons (IFNs), which include 14 IFN-α's and a single IFN-β, bind to this receptor complex to initiate signaling cascades that are pivotal for antiviral, antiproliferative, antiangiogenic, and immunomodulatory activities [1,2,4,5]. These activities are essential for innate and adaptive immune responses against viruses and other pathogens [4]. Genetic models, such as knockout mouse models, have been instrumental in studying Ifnar2's functions.

In Ifnar2 -/- mice infected with influenza A virus (IAV), increased and accelerated morbidity and mortality were observed compared to wild-type mice, indicating that Ifnar2 is critical for anti-viral immunity [5]. IFNAR2 was also sufficient to generate protection from lethal IAV infection when stimulated with IFN-β [5]. Additionally, knockdown of Ifnar2 in a mouse model of type 1 diabetes (T1D) reduced the inflammatory response and improved islet function, as IFNAR2 protein expression and inflammatory markers were decreased in these mice [3]. In the context of COVID-19, genetic variants in the IFNAR2 gene have been associated with disease severity and mortality risk among patients with severe COVID-19 [2].

In conclusion, Ifnar2 plays a vital role in anti-viral immunity, as demonstrated by gene-knockout mouse models in influenza and T1D studies. In the case of COVID-19, its genetic variants are linked to disease outcomes. Understanding Ifnar2's functions through these model-based studies provides insights into the immune response mechanisms and potential therapeutic targets for related diseases.

References:

1. López-Bielma, María Fernanda, Falfán-Valencia, Ramcés, Abarca-Rojano, Edgar, Pérez-Rubio, Gloria. 2023. Participation of Single-Nucleotide Variants in IFNAR1 and IFNAR2 in the Immune Response against SARS-CoV-2 Infection: A Systematic Review. In Pathogens (Basel, Switzerland), 12, . doi:10.3390/pathogens12111320. https://pubmed.ncbi.nlm.nih.gov/38003785/

2. Fricke-Galindo, Ingrid, Martínez-Morales, Alfonso, Chávez-Galán, Leslie, Guzmán-Guzmán, Iris Paola, Falfán-Valencia, Ramcés. 2022. IFNAR2 relevance in the clinical outcome of individuals with severe COVID-19. In Frontiers in immunology, 13, 949413. doi:10.3389/fimmu.2022.949413. https://pubmed.ncbi.nlm.nih.gov/35967349/

3. 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/

4. 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/

5. 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/