Ifih1 gene dose effect reveals MDA5-mediated chronic type I IFN gene signature, viral resistance, and accelerated autoimmunity.

ABSTRACT: Type I IFNs (IFN-I) are normally produced during antiviral responses, yet high levels of chronic IFN-I expression correlate with autoimmune disease. A variety of viral sensors generate IFN-I in their response, but other than TLRs, it is not fully known which pathways are directly involved in the development of spontaneous immune pathologies. To further explore the link between IFN-I induced by viral pathways and autoimmunity, we generated a new transgenic mouse line containing multiple copies of Ifih1, a gene encoding the cytoplasmic dsRNA sensor MDA5 with proven linkage to diabetes and lupus. We show that MDA5 overexpression led to a chronic IFN-I state characterized by resistance to a lethal viral infection through rapid clearance of virus in the absence of a CD8(+) or Ab response. Spont

SUBMITTER: Crampton SP 

PROVIDER: S-EPMC3262963 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature