| Project/Area Number |
16390613
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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 |
Periodontal dentistry
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| Research Institution | Niigata University |
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Principal Investigator |
YAMAZAKI Kazuhisa Niigata University, Institute of Medicine and Dentistry, Professor, 医歯学系, 教授 (00182478)
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| Co-Investigator(Kenkyū-buntansha) |
AMIZUKA Norio Niigata University, Center for Transdisciplinary Research, Professor, 超域研究機構, 教授 (30242431)
NAKAJIMA Takako Niigata University Medical and Dental Hospital, Clinical Education Unit, Lecturer, 医歯学総合病院, 講師 (40303143)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,200,000 (Direct Cost: ¥14,200,000)
Fiscal Year 2006: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2005: ¥5,100,000 (Direct Cost: ¥5,100,000)
Fiscal Year 2004: ¥4,900,000 (Direct Cost: ¥4,900,000)
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| Keywords | Regulatory T cells / FOXP3 / T-cell clone / Periodontitis / 炎症性サイトカイン / 抗炎症性サイトカイン / mRNA |
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| Research Abstract |
Periodontitis lesion is characterized by connective tissue destruction and alveolar bone resorption. The lesion contains large numbers of B lymphocytes and plasma cells together with significant numbers of T lymphocytes. We have previously found that the some of the T-cells in the lesion recognize auto-antigens such as heat-shock protein 60 and the response to such antigens play important roles in the pathogenesis of periodontitis. T-cell population can be classified into several distinct subsets functionally as well as phenotypically. In order to elucidate the role of various T-cell subsets in the pathogenesis of periodontal diseases, we comprehensively analyzed the periodontitis lesion-infiltrating T cells using immunological and molecular biological techniques.
The results demonstrated that a fraction of CD4^+ T cells expressed both CTLA-4 and CD25. CD4^+CD25^+CTLA-4^+ T cells are thought to be characteristic of natural regulatory T cells (Tr) and the percentage of CD4^+CD25^+ Tr cel
… More
ls increased with increasing proportions of B-cells relative to T-cells in periodontitis. Gene expression analysis showed that FOXP3, a characteristic marker for CD4^+CD25^+ Tr cells, TGF-β1 and IL-10 were expressed higher in periodontitis than gingivitis. Furthermore, it is demonstrated that another regulatory T cells called NKT cells which has been implicated in periodontitis are activated by CD Id-restricted manner and this NKT cell activation may mediate suppression of auto-reactive T cells.
In order to further analyze the role of T cells in the lesion, we established T-cell clones from the gingival tissues of periodontitis patients and examined the effecter function and their gene expression. Most but not all the T-cell clones from gingival tissues expressed mRNA for IFN-γ, IL-4, CD25 and CTLA-4. The frequency of T-cell clones expressing FOXP3 was very high. However, expressions of genes for IL-17 and RANKL, both of which are involved in the bone resorption, were variable among the T-cell clones.
Clonal analysis of the T cells clearly demonstrated the presence of T-cell populations reactive to human HSP60 and P. gingivalis GroEL in the peripheral circulation of atherosclerosis patients. These T-cells had been detected in the gingival tissues of periodontitis patients. Furthermore, these HSP60-reactive T cells seemed to be present in atherosclerotic lesions in some patients.
In conclusion, periodontitis lesion-infiltrating T cells may be involved in the pathogenesis of not only periodontal diseases but also atherosclerosis. Less
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