title: CD8(+) T cell-mediated skin disease in mice lacking IRF-2, the transcriptional attenuator of interferon-alpha/beta signaling.
abstract: The balanced action of cytokines is known to be critical for the maintenance of homeostatic immune responses. Here, we report the development of an inflammatory skin disease involving CD8(+) T cells, in mice lacking the transcription factor, interferon regulatory factor-2 (IRF-2). CD8(+) T cells exhibit in vitro hyper-responsiveness to antigen stimulation, accompanied with a notable upregulation of the expression of genes induced by interferon-alpha/beta (IFN-alpha/beta). Furthermore, both disease development and CD8(+) T cell abnormality are suppressed by the introduction of nullizygosity to the genes that positively regulate the IFN-alpha/beta signaling pathway. IRF-2 may represent a unique negative regulator, attenuating IFN-alpha/beta-induced gene transcription, which is necessary for balancing the beneficial and harmful effects of IFN-alpha/beta signaling in the immune system.
authors: Department of Immunology, Faculty of Medicine and Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
authors: S
authors: S
authors: Hida
authors: K
authors: K
authors: Ogasawara
authors: K
authors: K
authors: Sato
authors: M
authors: M
authors: Abe
authors: H
authors: H
authors: Takayanagi
authors: T
authors: T
authors: Yokochi
authors: T
authors: T
authors: Sato
authors: S
authors: S
authors: Hirose
authors: T
authors: T
authors: Shirai
authors: S
authors: S
authors: Taki
authors: T
authors: T
authors: Taniguchi
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D050836:Interferon Regulatory Factor-2; D007372:Interferons / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D012097:Repressor Proteins; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D012871:Skin Diseases / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology
chemical_list: D004268:DNA-Binding Proteins; D050836:Interferon Regulatory Factor-2; C494230:Irf2 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors; D007372:Interferons