| Project/Area Number |
17607011
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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 |
アレルギー
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| Research Institution | Saitama Medical University |
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Principal Investigator |
MATSUSHITA Sho Saitama Medical University, Faculty of Medicine, Professor., 医学部, 教授 (50167649)
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| Co-Investigator(Kenkyū-buntansha) |
UEMURA Yasushi Saitama Medical University, Faculty of Medicine, Assistant Professor., 医学部, 講師 (40364781)
KAISHO Tsuneyasu RIKEN, Japan, Research Center for Allergy and Immunology, Laboratory for Host Defense, Team Leader., 生体防御チーム, チームリーダー (60224325)
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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 |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Th2 cells / dendritic cells / adjuvants / Notch ligands / Jagged / Delta / estrogen / dopamine / TN2細胞 |
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| Research Abstract |
Dendritic cells (DCs) play a pivotal role in the differentiation of naive CD4^+ T helper cells towards either T helper 1 (Th1) or Th2 cells. Imbalances of these cell types are responsible for many diseases, including autoimmunity, cancer and asthma. However, the detailed mechanisms for Th1/Th2 polarization through the interaction between DCs and naive T cells remain obscure. We herein show that Th1/Th2 differentiation is controlled by dopamine, which is known to be a neurotransmitter. DCs synthesize dopamine, which is stored in the secretary vesicles and released after antigen-Specific interaction with naive CD4^+ T cells, thus resulting in dopamine-dependent Th2 polarization. Futhermore, antagonizing dopamine receptor subtypes differentially affected Th1/Th2 polarization both in vitro and in vivo. Unexpectedly, D2-like antagonists judged to be Th2 adjuvants in vitro caused a deterioration in the experimental autoimmune encephalomyelitis (EAE), an organ-specific autoimmune disease, whereas D1-like antagonists exhibited a marked improvement of EAE by inducing the Th1 response both in preventable and therapeutic protocols. These findings indicate that DA functions as an "Immunotransmitter" in DC-naive T cell interface to polarize Th2 differentiation, and will lead to the development of more effective strategies for the treatment of many diseases attributable to an imbalance of Th1/Th2.
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