Tracking interferon in autoimmunity

Abstract

Type I interferon is a family of antiviral cytokines linked to human autoimmune diseases. In this issue of Immunity, Gall et al. (2012) characterize, in a murine model of autoimmunity, the origin and progression of the type I interferon response leading to disease.

Figure 1. Myocarditis and Nephritis in TREX1-Deficient Mice Are Type I IFN- and Lymphocyte Dependent

Absence of TREX1 in nonhemopoietic results in cell-intrinsic activation of yet uncharacterized cytosolic DNA sensors. These sensors signal through STING-TBK1, leading to the phosphorylation and nuclear translocation of IRF3 and subsequent transcription of type I IFN genes. Unabated type I IFN production is necessary, but not sufficient to cause inflammation in Trex1^−/− mice. Lymphocytes are the mediators of inflammation, given that Trex1^−/− Rag2^−/− mice are disease free. Type I IFN-exposed T cells induce inflammation and fibrosis in the heart (myocarditis) as well as in the interstitial areas of the kidneys of Trex1^−/− mice. B cells and autoantibodies contribute to enhance the autoimmune pathology.