IRF-5 - A New Link to Autoimmune Diseases

Transcription factors of the interferon regulatory factor (IRF) family have a critical role in the activation of interferon (IFN) genes. All cellular IRFs share a region of homology in the amino terminus encompassing a highly conserved DNA binding motif characterized by five tryptophan repeats, but show variability in the carboxy (C-) terminal part of the IRF polypeptides. While some of these IRFs like IRF-3 and IRF-7 have a critical role in the antiviral response, the others like IRF-1, IRF-4 and IRF-8 have basic roles in the development and function of lymphoid cells. Recently, the importance of IRF-5 in the antiviral and inflammatory response in vivo has been clearly established, but it was also shown that this IRF has a basic function in apoptosis and B cells and macrophage differentiation. More interestingly, the role of IRF-5 pathogenicity in autoimmune diseases has been also established, as IRF-5 has been identified as one of the primary risk factors associated with Systemic Lupus Erythematosus (SLE) and other autoimmune diseases. This chapter will review the current knowledge of the mechanisms of IRF-5 activation by the TLR7 pathway and the genetic modifications of IRF-5 that may contribute to the dysregulation of the innate and adaptive immune response associated with the autoimmune disease. Furthermore we will summarize the contribution of the SLE mouse models to our understanding of the role of IRF-5 and TLR7 in the induction of the autoimmune diseases.