| Project/Area Number |
15590057
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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 |
Biological pharmacy
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| Research Institution | The University of Tokyo |
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Principal Investigator |
MATSUMOTO Naoki The University of Tokyo, Graduate School of Frontier Sciences, Associate Professor, 大学院新領域創成科学研究科, 助教授 (40239108)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Kazuo The University of Tokyo, Graduate School of Frontier Sciences, Professor, 大学院新領域創成科学研究科, 教授 (20174782)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2003: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | NK cells / T cells / Innate immunity / Lectin-like receptors / KLRG1 / ligand / cadherins / expression cloning / 可溶型レセプター / レセプター / 性状解析 |
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| Research Abstract |
Bodies of the metazoan organisms are protected by the immune system. The immune system of vertebrates consists of acquired and innate immunity. Natural killer (NK) cells play pivotal roles in innate immunity especially against cancer cells and intracellular pathogens. NK cell recognition of targets involves NK cell receptors with opposing functions: inhibitory receptors and activating receptors. Balance of signals from these receptors decides activation of NK cells. Most of the known ligands for the inhibitory NK cell receptors are MHC class I molecules, which are considered as markers of self. However, NK cell recognition of targets is not solely depend on MHC class I. Indeed, NK cells express inhibitory receptors of which ligands are unidentified, which include KLRG1. KLRG1 is a lectin-like inhibitory receptor expressed on subsets of NK and T cells. Expression of KLRG1 is also regulated by infection. In the present study, our group identified three classical cadherins, which contribute to cell-cell adhesion through homotypic interaction, as ligands for KLRG1. We also showed that ligation of KLRG1 by E-cadherin inhibit NK cell ctyotoxocity. Because the classical cadherins that KLRG1 recognizes are distributed ubiquitously among the body, KLRG1 may contribute to the termination of immune response induced by infection. The notion that expression of E-cadherin is often lost or attenuated in malignant carcinoma raises a possibility that KLRG1-expressing NK cells may play a role in malignant tumor surveillance. The current study provides a new concept that cadherins contribute to regulation of immune response through recognition by KLRG1.
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