Negative regulation of type I interferon signaling: facts and mechanisms.

Initially described for their antiviral activities, type I Interferons are now recognized as central regulatory elements of the immune response, primarily for their effect on the differentiation of monocytes into dendritic cells and osteoclasts. They are routinely used in clinic for the treatment of several diseases, including viral hepatitis, multiple sclerosis and several forms of cancer. Interferons are however not devoid of toxic effects when high doses are administered to patients, indicating that interferon action must be timely and spatially down regulated. We review here the molecular mechanisms which have been described to shut off the interferon initiated signals.