CD8(+) T cell-mediated skin disease in mice lacking IRF-2, the transcriptional attenuator of interferon-alpha/beta signaling.
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.
Hida
S
S
Department of Immunology, Faculty of Medicine and Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
Ogasawara
K
K
Sato
K
K
Abe
M
M
Takayanagi
H
H
Yokochi
T
T
Sato
T
T
Hirose
S
S
Shirai
T
T
Taki
S
S
Taniguchi
T
T
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
D004268:DNA-Binding Proteins; D050836:Interferon Regulatory Factor-2; C494230:Irf2 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors; D007372:Interferons