2006 Fiscal Year Final Research Report Summary
Signal transducing pathways in immune cells and immunological disorders caused by their dysfunctions
| Project/Area Number |
14104011
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| Research Category |
Grant-in-Aid for Scientific Research (S)
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| Allocation Type | Single-year Grants |
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| Research Field |
Immunology
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| Research Institution | Tohoku University |
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Principal Investigator |
SUGAMURA Kazuo Tohoku Univ., Grad Sch.of Med, Professor, 大学院医学系研究科, 教授 (20117360)
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| Co-Investigator(Kenkyū-buntansha) |
ISHII Naoto Tohoku Univ., Grad Sch. of Med, Associate Professor, 大学院医学系研究科, 助教授 (60291267)
TANAKA Nobuyuki Miyagi Cancer Center, Dept.of Immunol., Director, 免疫学部, 部長 (60280872)
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| Project Period (FY) |
2002 – 2006
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| Keywords | Cytokine / vesicle trafficking / T cell costimulatory signal / CD4 T cell / Inflammation |
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| Research Abstract |
1.Immune regulation by intracellular vesicular trafficking
STAM1 and STAM2 are required for the ubitquitin-dependent sorting of protein cargos into multivesicular bodies. Using genetically manipulated mice, in which both STAM1 and STAM2 are lacking specifically in dendritic cells, we found that STAM1/2 play an important role in antigen presentation. In vitro analyses demonstrated that STAM1/2-double KO dendritic cells show aberrant intracellular localization of MHC II and overexpression of surface MHC II. Therefore, STAM1/2 is thought to critically regulate MHC II trafficking from intracellular vesicular compartments to the plasma membrane.
2.Autoimmune diseases mediated by T cell costimulatory signals
We previously reported that mice overexpressing OX40 ligand (OX4OL), which is a T-cell-costimulatory molecule expressed by antigen presenting cells, spontaneously develop IBD. A mechanism for IBD development in the OX40L-transgenic (Tg) mice may be mediated by excessive OX40 signals in CD4^+ T cells because deliberate OX40-0X4OL interaction makes effector CD4^+ T cells insensitive to regulatory-T-cell-mediated suppression, which is an important mechanism to maintain the homeostasis of mucosal immunity. Although this abnormal T cell response in OX40L-Tg mice was seen in all the mouse strains we used, IBD develops in a C57BL/6 strain-dependent manner. Thus, we have attempted to identify susceptibility genes for IBD seen in OX40L-Tg mice. A QTL analysis using the susceptible strain (C57BL/6) and a resistant strain (BALB/c) revealed three disease-associated loci on Ch. 4,Ch. 8,and Ch. 19. From these loci, we have identified a candidate susceptibility gene for IBD.
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Research Products
(12 results)
