Determining the source of Type III IFNs (IFNλs) in vivo using a novel IFNλ reporter mouse model — ASN Events
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  3. Determining the source of Type III IFNs (IFNλs) in vivo using a novel IFNλ reporter mouse model

Determining the source of Type III IFNs (IFNλs) in vivo using a novel IFNλ reporter mouse model (#327)

Marvin J Sandoval 1 , Russell K Durbin 2 , Sergei V Kotenko 3 , Joan E Durbin 2
  1. Pathology, NYU School of Medicine, New York, NY, USA
  2. Pathology, Rutgers-New Jersey Medical School, Newark, NJ, USA
  3. Biochemistry, Rutgers-New Jersey Medical School, Newark, NJ, USA

Similar to Type I IFNs (IFNα/β), Type III IFNs (IFNλ1,2,3,4) exert antiviral and antiproliferative effects through a JAK-STAT mediated pathway that activates ISGF3 (STAT1/STAT2/IRF9) and consequently induces the expression of interferon-stimulated genes (ISGs).  IFNλs signal through a receptor complex distinct from that of IFNα/β, composed of IL10R2 and IFNλR1, which appears to be preferentially expressed on epithelial cells and certain immune cell subsets.  Accumulating evidence suggests that IFNλs play a major role in protecting the host from viruses targeting the mucosal surfaces of the respiratory and gastrointestinal tracts as well as the liver.  Like type I IFNs, IFN-λs are produced by various cell types in response to virus infection or TLR ligand stimulation, via mechanisms that appear to be similar but not identical.  The major cell populations contributing to the production of IFNλs in vivo, in response to specific viral pathogens, remain unclear. To gain a clearer picture of the source(s) of type III IFNs in the course of virus infection, we have generated a novel IFNλ reporter mouse (IFNλ2+/eGFP), in which one allele of the IFN-λ2 coding sequence has been replaced with eGFP by homologous recombination, while maintaining the IFN-λ2 promoter regions and UTRs intact.  Thus, any cell from this mouse that produces IFN-λ2 will also express eGFP, allowing us to identify and isolate IFNλ-producing cells present within tissues as an infection progresses.  Preliminary studies using FLT3L and GMSCF cultured, bone marrow-derived dendritic cells from these mice show that a subpopulation of dendritic cells produce IFN-λ in response to Newcastle disease virus infection, and characterization of these cells, including their role as type III IFN producers, is now underway. It is anticipated that the availability of the IFNλ2+/eGFP reporter mouse will help in the identification of IFN-λ producing cells in response to various viral infections in vivo and ultimately aid in understanding the distinct role IFNλs play in antiviral immunity.