| Project/Area Number |
22390098
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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 |
Immunology
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| Research Institution | Research Institute, International Medical Center of Japan |
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Principal Investigator |
SUZUKI Harumi 独立行政法人国立国際医療研究センター, 免疫病理部, 部長 (70235985)
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| Co-Investigator(Kenkyū-buntansha) |
HAYAKAWA Kunihiro 国立国際医療研究センター, 免疫病理, 研究員 (00573007)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2012: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2010: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
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| Keywords | リンパ球 / 胸腺 / T細胞 / 分化 / シグナル伝達 / 正の選択 / 自己免疫 |
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| Research Abstract |
We identified a novel gene Gasp (Themis), which is exclusively expressed in the thymus and reported that Themis is critical in positive selection of thymocytes. Themis is a unique molecule that is absolutely required for positive selection, but is not required for negative selection and homeostatic expansion. Themis constitutively associates with Grb2 and tyrosine phosphorylated upon TCR-stimulation, therefore likely to be involved in TCR-dependent signal transduction. It is also involved in TCR-dependent IL-2 production, however, we could not observe any sign of modulating signaling strength. From domains deletion analysis of Themis, two of CABIT domains, a proline rich sequence (PRS), and a nuclear localization signal (NLS) are all shown to be required for its function. Collectively, Themis is not simply modulating strength of signal, but may be important for sustaining weak signal required for positive selection in the thymus. Molecular mechanism of Themis is still not well known, however, the current study unveiled its importance for IL-2 production, and differential function of the two CABIT domains. Themis may not simply modulate signaling strength like other signal transducers, but it may involved in spatiotemporal regulation of intracellular signal transduction.
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