| Project/Area Number |
10670311
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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 |
Immunology
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| Research Institution | Chiba University |
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Principal Investigator |
NAKAYAMA Toshinori Chiba University, Graduate School of Medicine, Associate Professor, 大学院・医学研究科, 助教授 (50237468)
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| Project Period (FY) |
1998 – 1999
|
| Project Status |
Completed (Fiscal Year 1999)
|
| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Th1 / Th2 / Ras / MARK cascade / allergy / T cell receptor / IL-4 / ヘルパーT細胞 / ドミナントネガティブ |
|---|
| Research Abstract |
The central role of Type-2 helper T (Th2) cells in the development of allergic responses and immune responses against helminthic parasites is well documented. The differentiation of Th2 cells from naive T cells requires both the recognition of antigen by T-cell antigen receptors (TCR) and the activation of downstream signal transduction molecules of the IL-4 receptor (IL-4R) pathway, including Jak1, Jak3, and STAT6. Little is known, however, about how these two distinct pathways cooperate with each other to induce Th2 cells. Here we use a T cell specific H-ras-dominant negative transgenic mouse to show that TCR-mediated activation of Ras/Mitogen-activated protein kinase (MAPK) pathway alters IL-4R function and is required for Th2 cell differentiation. The enhancement of IL-4R signaling appears to be a consequence of both direct crosstalk with the TCR signaling pathway and increased protein expression of downstream signaling molecules of the IL-4R pathway. Therefore, successful Th2 differentoation depends on the effectiveness of the TCR-mediated activation of the Ras/MAPK pathways in modifying the IL-4R-mediated signaling pathway. In another words, we present evidence that the TCR-mediated Ras/MAPK activation controls IL4R-mediated signaling and determines the direction of helper T cell differentiation. Thus, our data suggest that the lineage choices made by naive Th cells following antigen, stimulation are clearly influenced by.
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