Regulation and Dynamics of IFN-β Expression Revealed with a Knockin Reporter Mouse

Area of Science:

• Immunology
• Virology
• Genetics

Background:

• Interferon-beta (IFN-β) is a crucial type I cytokine in antiviral responses, but tools to study its induction and behavior are limited.
• IFN-β has both protective roles in viral infections and pathogenic roles in autoimmune and autoinflammatory diseases.
• Understanding IFN-β dynamics is essential for both infectious disease and autoimmune research.

Purpose of the Study:

• To develop a novel reporter mouse model for tracking IFN-β-expressing cells.
• To enable detailed studies on the induction, kinetics, and cellular behavior of IFN-β.
• To provide a tool for investigating the biological roles of IFN-β in host defense and disease.

Main Methods:

• Generation of a knockin mouse model with an Ifnb-IRES-TdTomato-Cre reporter.
• Demonstration of pathway-specific induction of the TdTomato reporter.
• Utilizing the Cre recombinase for permanent marking of IFN-β expressing cells.
• In vivo Sendai virus infection model in mice.

Main Results:

• The reporter mouse model successfully tracks IFN-β-expressing cells.
• MAVS-dependent IFN-β response was identified in lung epithelial cells post-Sendai virus infection.
• Activation of RNase L by RIG-I-like receptor ligands inhibits IFN-β and reporter protein translation in macrophages.
• The Cre recombinase permanently marks cells that have expressed IFN-β.

Conclusions:

• The Ifnb-IRES-TdTomato-Cre reporter mouse is a valuable tool for studying type I Interferon biology.
• This model facilitates research into IFN-β induction, antiviral responses, and its role in disease.
• The findings highlight the complex regulation of IFN-β production and its inhibition by RNase L activation.