2006 Fiscal Year Final Research Report Summary
The development of an innovative therapy for autoimmune diseases by controlling FOXP3, a unique transcription factors of the regulatory T cells
| Project/Area Number |
17591032
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
膠原病・アレルギー・感染症内科学
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| Research Institution | The University of Tokyo |
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Principal Investigator |
MISAKI Yoshikata The University of Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (60219615)
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| Co-Investigator(Kenkyū-buntansha) |
KAWAHATA Kimito The University of Tokyo, Faculty of Medicine, Assistant Professor, 医学部附属病院, 助手 (70334406)
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| Project Period (FY) |
2005 – 2006
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| Keywords | regulatory T cell / yeast two hybrid / retrovirus vector / transcription factor / autoimmune disease |
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| Research Abstract |
CD4(+) CD25(+) regulatory T cells (Treg) contributes in homeostasis of the immune system by controlling an immune response. Accumulating studies indicate that the control in the number or function of Treg lead to innovation in the treatment of autoimmune diseases. Recently, FOXP3 was identified to be a unique transcription factor for Treg. In order to understand the functional mechanism of FOXP3, we conducted two yeast hybrid screening, and found that SOCS1 and 3 are the partner candidates of FOXP3. In this study we found that endogenous SOCS3 was co-immunoprecipitated with FLAG-tagged FOXP3 in FOXP3-transfected Treg cell clone, indicating that SOCS3 is associated with FOXP3. However, RNA silencing of either SOCS1 or SOCS3 by shRNA expressed by retroviral vector did not reveal a distinct alternation in the suppressive activity of Treg. Although our result would be due to the relatively higher expression of FOXP3 in comparison with the decrease of SOCS expression by targeting, SOCS3 might not contribute in the regulatory activity of FOXP3. Rather, as is known that Treg development is disturbed in SOCS1-deficient mice and that SOCS family contribute in the protein degradation via ubiquitin-ligase activity, SOCS3 might play some role in the development of T cells in the thymus or degradation of Foxp3 in effector T cells.
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