In rodent models of experimentally induced arthritis, HMGB1 is an essential mediator of inflammation and joint destruction as HMGB1-blocking therapies ameliorate both the inflammatory and tissue destructive disease course in collagen-induced arthritis and the spontaneous arthritis developing in DNAseII x IFNR1 deficient mice 18–22. Here, IFNAR1 is linked to arthritic joint disease.