2005 Fiscal Year Final Research Report Summary
The importance of the deletion of RP105 on B cells in autoimmune diseases and its application for the treatment
| Project/Area Number |
16590985
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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 | Saga University |
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Principal Investigator |
NAGASAWA Kohei Saga University, Faculty of Medicine, Professor, 医学部, 教授 (00108721)
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| Co-Investigator(Kenkyū-buntansha) |
KOARADA Syuichi Saga University, Faculty of Medicine, Instructor, 医学部, 助手 (50304887)
TADA Yoshifumi Saga University, Faculty of Medicine, Instructor, 医学部, 講師 (70284627)
KIMOTO Masao Saga University, Faculty of Medicine, Professor, 医学部, 教授 (40153225)
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| Project Period (FY) |
2004 – 2005
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| Keywords | RP105 / B cell / Autoimmune disease / SLE / Sjogren's syndrome / Autoantibody / Collagen arthritis / Microalley |
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| Research Abstract |
RP105 was first identified on murine B cells in 1994 and it was found to be closely associated with the proliferation or apoptosis of B cells. We have previously demonstrated that the proportion of peripheral blood B cells lacking RP105 was significantly increased in patients with systemic lupus erythematosus(SLE), Sjogren's syndrome (SS) and dermatomyositis (DM). Importantly, those RP105(-) B cells were found to be highly activated and differentiated and produce autoantibodies such as anti-DNA antibody.
With the above background, we obtained the results in this study as follows.
1)The infiltration of RP105(-) B cells were dominant in the salivary gland in SS patients and was correlated with the serum level of immunoglobulins(Ig), suggesting that those B cells may be associated with the production of Ig and tissue damage of salivary gland.
2)The expression of Toll-like receptor(TLR) 4, a related molecule of RP105, was increased in monocytes from patients with acute infectious diseases and SLE. The association of infectious diseases and autoimmune diseases is under investigation through these molecules.
3)We made genetically RP105-deleted mice and investigated the development of collagen-induced arthritis (CIA), a model of rheumatoid arthritis. It was found that the incidence and severity of CIA was increased in RP105-deleted mice, suggesting that RP105 might have a regulatory function against excessive immune response.
4)For the approach to a new treatment of autoimmune diseases, we are searching for molecules specifically expressed on RP105(-) B cells using DNA microalley method. We have found a few candidate molecules that are still under investigation.
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