Ifnl2-KO Mouse

Ifnl2, a member of the interferon lambda (IFN-λ) family, is a potent antiviral interferon. Type III interferons, including Ifnl2, are involved in the innate immune response, especially in mucosal antiviral defense. They signal via the IFN-λ receptor (IFNLR) and play a role in multiple cellular functions related to immune response [2,3].

Disruption of both Ifnl2 and Ifnl3 genes in mice recapitulates the loss of the IFNLR in mucosal antiviral responses. These Ifnl2-/- Ifnl3-/- mice display defective control of murine norovirus, reovirus, and influenza virus, indicating that IFNLR-mediated signaling at mucosal sites can be attributed to the activity of IFN-λ2 and IFN-λ3 [3]. Also, reduced levels of Ifnl2 in COVID-19 patients are associated with a worse disease outcome, suggesting its protective role against SARS-CoV-2 infection [1].

In summary, Ifnl2 is crucial for mucosal antiviral defense and likely plays a protective role against certain viral infections such as SARS-CoV-2. Gene knockout models of Ifnl2, especially in combination with Ifnl3, have been instrumental in revealing its role in mucosal antiviral responses, highlighting its importance in understanding and potentially combating viral diseases at mucosal surfaces.

References:

1. Woods, Elena, Mena, Adriana, Sierpinska, Sophie, Macallan, Derek, Gardiner, Clair M. . Reduced IFNL1 and/or IFNL2, but not IFNL3 is associated with worse outcome in patients with COVID-19. In Clinical and experimental immunology, 218, 300-307. doi:10.1093/cei/uxae047. https://pubmed.ncbi.nlm.nih.gov/38953458/

2. Cohen, Taylor S, Parker, Dane. 2016. Microbial pathogenesis and type III interferons. In Cytokine & growth factor reviews, 29, 45-51. doi:10.1016/j.cytogfr.2016.02.005. https://pubmed.ncbi.nlm.nih.gov/26987613/

3. Peterson, Stefan T, Kennedy, Elizabeth A, Brigleb, Pamela H, Boon, Adrianus C M, Baldridge, Megan T. 2019. Disruption of Type III Interferon (IFN) Genes Ifnl2 and Ifnl3 Recapitulates Loss of the Type III IFN Receptor in the Mucosal Antiviral Response. In Journal of virology, 93, . doi:10.1128/JVI.01073-19. https://pubmed.ncbi.nlm.nih.gov/31462571/