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.
Taki
Shinsuke
S
Department of Molecular Genetics, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670, Japan. shin-t@sch.md.shinshu-u.ac.jp
D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology / Q000503:physiopathology; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D006526:Hepatitis C / Q000188:drug therapy; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use; D050836:Interferon Regulatory Factor-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000502:physiology* / Q000627:therapeutic use; D016899:Interferon-beta / Q000009:adverse effects / Q000502:physiology* / Q000627:therapeutic use; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D018448:Models, Immunological; D009103:Multiple Sclerosis / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy; D010641:Phenotype; D051381:Rats; D017471:Receptors, Interferon / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D012097:Repressor Proteins; D012871:Skin Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology; D013577:Syndrome; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014157:Transcription Factors
D004268:DNA-Binding Proteins; C494229:IRF2 protein, human; D007155:Immunologic Factors; D050836:Interferon Regulatory Factor-2; D016898:Interferon-alpha; C494230:Irf2 protein, mouse; D017471:Receptors, Interferon; D012097:Repressor Proteins; D014157:Transcription Factors; D016899:Interferon-beta