2007 Fiscal Year Final Research Report Summary
Induction of polyclonal IgE response by LPS-stimulated basophils
| Project/Area Number |
17390145
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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 | Hyogo College of Medicine |
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Principal Investigator |
NAKANISHI Kenji Hyogo College of Medicine, Faculty of Medicine, Professor (60172350)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIMOTO Tomohiro Hyogo College of Medicine, Faculty of Medicine, Associate Professor (60241171)
TSUTSUI Hiroko Hyogo College of Medicine, Faculty of Medicine, Professor (40236914)
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| Project Period (FY) |
2005 – 2007
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| Keywords | basophils / TLR / IL-18 / IL-33 / APC / Th2 / IgE |
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| Research Abstract |
Basophils and mast cells are important effecter cells in allergic inflammation. Here we investigated whether these cells also induce allergic response by induction of Th2/IgE response. Many microbes express unique pathogen-associated molecular patterns (PAMPs). Upon entry of invading bacteria, DCs recognize them through TLRs and mature to express co-stimulatory molecules CD80 and CD86 and to produce IL-12, IL-18 and other proinflammatory cytokines. Thus, TLR-mediated signaling particularly favors the development and activation of Th1 response. In contrast, the role of innate immune cells in the development of Th2 response is poorly understood. Since basophils produce IL-4 in response to IL-3 plus IL-18, we first tested whether basophils express TLRs and produce IL-4 in response to TLR ligand. We found that both basophils and mast cells express TLR and only basophils produce IL-4 in response to IL-3 plus TLR ligands. We also found both types of cells express IL-18R and IL-33R and only b
… More
asophils produce IL-4 in response to IL-18 and/or IL-33 in the presence of IL-3, suggesting the potential of basophils to induce naive CD4+ T cells to develop into Th2 cells by production of IL-4. We next examined whether basophils express molecules that Ag-presenting cells express. Basophils express MHC class II, CD80 and CD86. Naive OVA-specific CD4+ T cells cultured with basophils and OVA peptide with IL-3 but without additional IL-4 developed into cells positive for cytoplasmic IL-4. This capacity of basophils to induce Th2 cells was almost completely abolished by addition of anti-IL-4 antibody, suggesting that IL-4 released from IL-3-stimulated basophils is critically involved in the development of Th2 cells. Then, we added native OVA or DNP-OVA instead of OVA peptide and found that basophile induced the development of OVA-specific naive CD4+ T cells into Th2 cells. Furthermore, basophil pulsed with DNP-OVA in the presence of anti-DNP IgE showed more efficient APC activity than basophils pulsed without anti-DNP IgE, suggesting positive feedback regulation of IgE response by IgE-dependent Ag internalization. Thus, basophils play critical role in induction of and augmentation of Th2/IgE response. Less
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Research Products
(17 results)
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[Journal Article] Type 1 cytokine/chemokine production by mouse NK cells following activation on their TLR/MyD88-mediated pathways2007
Author(s)
Sawaki, J., Tsutsui, H., Hayashi, N., Yasuda, K., Akira, S., Tanizawa, T. and Nakanishi, K.
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Journal Title
Int.Immunol 19・3
Pages: 311-320
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Interleukin-18 regulates T helper 1 or 2 immune responses of human cord blood CD4^+ Vα24^+Vβ1^+ natural killer T cells2007
Author(s)
Fujibayashi, Y., Fujimori, Y., Kasumoto, I., Kai, S., Hara, H., Okamura, H., Tsutsui, H., Ogawa, H. and Nakanishi, K.
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Journal Title
Int.J.Mol.Med. 20
Pages: 241-245
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] T helper 1 cells stimulated with ovalbumin and IL-18 induce airway hyperresponsiveness and lung fibrosis by IFN-γ and IL-13 production2007
Author(s)
Hayashi, N., Yoshimoto, T., Izuhara, K., Matsui, K., Tanaka, T. and Nakanishi, K.
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Journal Title
Proc.Natl.Acad.Sci.USA. 104
Pages: 14765-14770
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Interleukin-18 regulates T helper 1 or 2 immune responses of human cord blood CD4^+Vα24^+Vβ11^+ natural killer T cells.2007
Author(s)
Fujibayashi, Y., Ftriimori, Y., Kasumoto, I., Kai. S. Hara. H., Okamura, H., Tsutsui, H. Ozawa, H., Nakanishi, K.
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Journal Title
Int. J. Mol. Med. 20
Pages: 241-245
Description
「研究成果報告書概要(欧文)」より
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