| Project/Area Number |
17592071
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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 |
Surgical dentistry
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
KATOU Fuminori Hamamatsu University School of Medicine. Department of Oral and Maxillofacial Surgery, Associate Professor, 医学部, 助教授 (60204492)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Hideo Hamamatsu University School of Medicine, University Hospital. Department of Oral and Maxillofacial Surgery, Assistant Proffessor., 医学部附属病院, 助手 (30362205)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥800,000 (Direct Cost: ¥800,000)
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| Keywords | naive CD8+ T cells / homing / lymph node / dopamine receptor D3 / 口腔癌 / ケモカイン |
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| Research Abstract |
The nervous systems affect immune functions by releasing neurohormones and neurotransmitters. A neurotransmitter dopamine signals via five different seven transmembrane G protein-coupled receptors terms D1 to D5. The secondary lymphoid tissues are highly innervated by sympathetic nerve fibers that store dopamine at high contents. Lymphocytes also produce dopamine. Here, we examined expression and function of dopamine receptors in lymphocytes. We found that D3 was the predominant subtype of dopamine receptors in the secondary lymphoid tissues and selectively expressed by naive CD8^+ T cells of both human and mouse. Dopamine induced calcium flux and chemotaxis in mouse L1.2 cells stably expressing human D3. These responses were almost completely inhibited by pertussis toxin (PTX), indicating that D3 was coupled with the Gai class of G proteins. Consistently, dopamine selectively induced chemotactic responses in naive CD8^+ T cells of both human and mouse in a manner sensitive to PTX and D3 antagonists. Dopamine was highly synergistic with CCL19, CCL21, and CXCL12 in induction of chemotaxis in naive CD8^+ T cells. Dopamine selectively induced adhesion of naive CD8^+ T cells to fibronectin and ICAM-1 through activation of integrins. Intraperitoneal injection of mice with dopamine selectively attracted naive CD8^+ T cells into the peritoneal cavity. Treatment of mice with a D3 antagonist U-99194A selectively reduced homing of naive CD8^+ T cells into lymph nodes. Collectively, naive CD8^+ T cells selectively express D3 in both human and mouse, and dopamine plays a significant role in migration and homing of naive CD8^+ T cells via D3.
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