Inhibition of lupus by genetic alteration of the interferon-alpha/beta receptor.
Type I interferons (IFN-alphabeta) are immunoregulatory cytokines that promote both innate and adaptive immune responses. Although they have been implicated in human SLE, recent studies in mice have helped solidify this connection. By using lupus-prone mice with knockout of the IFN-alphabeta receptor, we and others have documented that lack of IFN-alphabeta leads to a marked reduction in disease manifestations, including autoantibody production, target organ damage and mortality. Furthermore, IFN-alphabeta was found to potentially contribute to several levels of disease pathogenesis. These included the differentiation and activation of dendritic cells, the activation and proliferation of T cells, T cell survival and the activation and survival of autoantibody-producing B cells. These findings strongly support the targeting of IFN-alphabeta in SLE and suggest that definition of the specific pathways critical for disease induction will be important for optimal intervention.
Kono
Dwight H
DH
Department of Immunology/IMM3, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA. dkono@scripps.edu
Baccala
Roberto
R
Theofilopoulos
Argyrios N
AN
D000818:Animals; D017951:Antigen Presentation; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology; D004268:DNA-Binding Proteins / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D007113:Immunity, Innate; D007370:Interferon Type I / Q000096:biosynthesis* / Q000276:immunology; D016898:Interferon-alpha / Q000096:biosynthesis / Q000502:physiology*; D016899:Interferon-beta / Q000096:biosynthesis / Q000502:physiology*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D051379:Mice; D008814:Mice, Inbred NZB; D017471:Receptors, Interferon / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D001323:Autoantibodies; D004268:DNA-Binding Proteins; D007370:Interferon Type I; D016898:Interferon-alpha; D017471:Receptors, Interferon; D016899:Interferon-beta