Type I interferons and autoimmunity: lessons from the clinic and from IRF-2-deficient mice.

Type I interferons (IFN-alpha/beta) are produced upon viral and bacterial infections and play essential roles in host defense. However, since IFN-alpha/beta have multiple regulatory functions on innate and adoptive immunity, dysregulation of the IFN-alpha/beta system both in uninfected hosts and during immune responses against infection can result in immunopathologies. In fact, IFN-alpha/beta therapy often accompanies autoimmune-like symptoms. In this regard, we have recently found that mice lacking IFN regulatory factor (IRF)-2, a negative regulator of IFN-alpha/beta signaling, develop spontaneous, CD8(+) T cell-dependent skin inflammation. This unique animal model, together with other animal models, highlights the importance of the mechanism maintaining the homeostasis in the IFN-alpha/beta system even in the absence of infection.