2003 Fiscal Year Final Research Report Summary
Development of a novel molecular therapy for rheumatoid arthritis by regulation of Th1/Th2 differentiation
| Project/Area Number |
14370167
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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 |
内科学一般
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| Research Institution | University of Tsukuba (2003)
The Institute of Physical and Chemical Research (2002) |
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Principal Investigator |
SHIBUYA Kazuko University of Tsukuba, Institute of Basic Medical Science, Assistant Professor, 基礎医学系, 講師 (00302406)
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| Co-Investigator(Kenkyū-buntansha) |
IWAMA Atsushi University of Tokyo, Institute of Medical Science, Assistant Professor, 医科学研究所, 講師 (70244126)
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| Project Period (FY) |
2002 – 2003
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| Keywords | autoimmune response / rheumatoid arthritis / Th1 cells / Th2 cells / differentiation of Th1 / Th2 cells / independency of cytokines / LFA-1 / CD226 |
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| Research Abstract |
Because Th1 cells are implicated in the immunopathology of rheumatoid arthritis, an understanding of molecular mechanisms of Th1fTh2 differentiation is required for development of a new therapy for rheumatoid arthritis, Th1 and Th2 cells are derived from CD4 positive naive T cells. Because CD4 positive naive T cells require intercellular binding with antigen presenting cells for differentiation of helper T cells, we investigated whether intercellular adhesion molecules on CD4 positive naive T cells may play an important role for initial triggering of differentiation of helper T cells
Here, we report that cross-linking of LFA-1 and CD3 drives Th1 differentiation from CD4 positive naive T cells from peripheral blood or cord blood cells. Addition of anti-IL-12 neutrarizing antibody did not inhibit the Th1 differentiation induced by stimulation of LFA-1. These results indicate that Th1 differentiation mediated by LFA-1 is independent on IL-12. Furthermore, we, show that lentiviral vector-mediated mutant (Y-F^<322>) CD226 transfer into naive CD4^+ helper T cells inhibited IL-12-independent Th1 differentiation initiated by CD3 and LFA-1 ligations. These results suggest that CD226 is involved in LFA-1-mediated costimulatory signals for triggering nave T helper cell differentiation
In future, we will investigate the relationship between LFA-1/CD226-mediated Th1 differentiation and the immunopathology of rheumatoid arthritis using mice with the collaoen-induced arthritis, a model for rheumatoid arthritis
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Research Products
(13 results)
