Analyses of the immunoregulatory mechanisms by IL-12-related cytokines and their receptors
| Project/Area Number |
16390145
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | Saga University |
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Principal Investigator |
YOSHIDA Hiroki Saga University, Faculty of Medicine, Professor, 医学部, 教授 (40260715)
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| Co-Investigator(Kenkyū-buntansha) |
濱野 真二郎 九州大学, 大学院・医学系研究科, 助手 (70294915)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 2005: ¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 2004: ¥7,700,000 (Direct Cost: ¥7,700,000)
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| Keywords | IL-27 / CD4+T cells / inflammation / Infection / autoimmunity / cytokines / Th1 / lymphocyte differentiation / WSX-1 / 感染症 / 自己免疫疾患 |
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| Research Abstract |
Cytokine/cytokine receptor network is critical in the establishment of immune reaction against various pathogens. We have generated a line of mice deficient for IL-27 receptor (WSX-1) gene and have proved that the mice show remarkable susceptibility against Leishmania major infection by impaired IFN-gamma production. By additional elucidation of the signal transduction mechanisms downstream of IL-27R, we have shown that IL-27/IL-27R (WSX-1) is critical in the initial commitment of Th1 differentiation, prior to IL-12. In addition, IL-27/WSX-1 is also shown to have immunoregulatory function by suppression of pro-inflammatory cytokine production during some protozoan infection. In the current study, we further analyzed the immunoregulatory roles of IL-27 and reported that, due to the augmented inflammatory responses in the absence of IL-27 signaling, allergic asthma exacerbated and also that lethal systemic inflammation occurred during Mycobacterium tuberculosis infection. In MRL/lpr mice, which develop human systemic lupus erythematosus-like autoimmune disease, lack of IL-27R was accompanied with membranous glomerulonephritis (MGN), instead of diffuse proliferative glomerulonephritis in the wild-type mice. To the best of our knowledge, this is the first presentation of a line of model mice that spontaneously develop MGN. For the dual roles of IL-27, we also examined the signal transduction mechanisms and have found that, for Th1 induction, STAT1 activation is critical and that, for immunoregulation, STAT3 activation is important ; further elucidation of the roles and mechanisms of IL-27 is required for therapeutic application of IL-27.
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Report
(3 results)
Research Products
(34 results)
