Interferon-inducible gene expression in dermatomyositis muscle

Gene expression profi ling of peripheral blood or aff ected tissues in patients with autoimmune diseases has revealed important insights into the molecular pathways underlying autoimmunity [1]. Several groups have used gene expression profi ling in an attempt to uncover clues to the pathogenesis of dermatomyositis (DM) (Table 1). Th e most prominent and consistent fi nding of these studies has been the presence of a gene signature characteristic of type I interferon (IFN) pathway activation, discovered fi rst in DM muscle tissue and later identifi ed in peripheral blood cells. Th e identifi cation of IFN occurred over 50 years ago when IFN was observed to be produced in response to viral illnesses. More recently, type I IFNs have been identi fi ed as an important mediator in autoimmune diseases including juvenile dermatomyositis (JDM) and adult dermatomyositis (ADM). Th ere are at least three classes of IFNs, including what are referred to as type I IFNs, which in humans include 13 subtypes of IFNα, IFNβ, IFNω, IFNε, and IFNκ. All of the type I IFNs are thought to signal through the same receptor, type I IFN receptor. Other IFNs have been seen in autoimmune disorders, including DM, such as type II IFN (IFNγ) that is mainly produced by natural killer cells and activated T cells (T-helper type 1 cells), and type III IFNs that are a newly discovered class consisting of three members – IFNγ1, IFNγ2, and IFNγ3 – which have overlapping activities with type I IFNs but signal through a distinct receptor [2].