title: Type-I interferons and systemic lupus erythematosus.
abstract: Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by the production of autoantibodies directed against nuclear antigens and chronic inflammation affecting multiple tissues. Complex genetic disorders are at the origin of the disease in humans and in SLE-prone mice, leading to the escape of auto-reactive B-lymphocytes from central and peripheral control checkpoints that operate normally in healthy organisms. Although necessary, autoimmune B-cells are not sufficient and additional mechanisms such as T-cell help are clearly needed for the disease to occur. The role of type-I interferons (type-I IFNs), and in particular IFNalpha, as prominent cofactors for SLE was suggested years ago. Leading observations in patients and recent data in SLE-prone mice have now established IFNalpha as a major actor in SLE. Several systemic clinical symptoms and laboratory findings can indeed be interpreted as downstream effects of a high IFNalpha production, and point to this cytokine as a link between the expansion of autoimmune B-cells and the stimulation of other components of the immune system. Consequently, a vicious circle is established with overt immune-cell activation and inflammatory infiltrates culminating in the selective destruction of tissue targets, notably the kidney. These notions can now be transplanted to the clinic and designate IFNalpha as a new promising therapeutic target.
authors.affiliation: INSERM U 764 and Université Paris XI, 32 Rue des Carnets, Clamart, France. sophie.koutouzov@inserm.ipsc.u-psud.fr
authors.forename: Sophie
authors.initials: S
authors.lastname: Koutouzov
authors.forename: Alexis
authors.initials: A
authors.lastname: Mathian
authors.forename: Ali
authors.initials: A
authors.lastname: Dalloul
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D007370:Interferon Type I / Q000502:physiology*; D008180:Lupus Erythematosus, Systemic / Q000209:etiology* / Q000276:immunology* / Q000503:physiopathology; D051379:Mice
chemical_list: D007370:Interferon Type I