SUPPRESSION OF EXPERIMENTAL AUTOIMMUNE UVEORETINITIS BY NEUROPEPTIDE GENE-TRANSFECT-CELLS
Project/Area Number |
17591855
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Ophthalmology
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Research Institution | TOKYO MEDICAL UNIVERSITY |
Principal Investigator |
KEZUKA Takeshi TOKYO MEDICAL UNIVERSITY, Medicine, ASSISTANT PROFESSOR, 医学部, 講師 (00287137)
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Co-Investigator(Kenkyū-buntansha) |
TAKEUCHI Masaru TOKYO MEDICAL UNIVERSITY, Medicine, ASSOCIATE PROFESSOR, 医学部, 助教授 (40260939)
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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: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2005: ¥2,900,000 (Direct Cost: ¥2,900,000)
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Keywords | CGRP / UVEITIS / GENE THERAPY / DENDRITIC CELL |
Research Abstract |
To investigate the role of the suppression in murine experimental autoimmune uveoretinitis (EAU) by mature dendritic cells (DC) cultured with calcitonin gene-related peptide (CGRP). Bone marrow cells derived from C57BL/6 mice were cultured with GM-CSF for six days, and differentiated CD11^+ immature DC were purified by autoMACS. Immature DC were further cultured with LPS (1 μg/ml) overnight, and then with human interphotoreceptor retinoid binding protein (IRBP) residues 1-20 (hIRBP-p) in the presence of CGRP or TGF-B2. EAU was induced by immunization with hIRBP-p in Freund' s adjuvant and pertussis toxin in mice. At the same time, hIRBP-p-immunized mice were injected the mature DC cultured with CGRP or TGF-B2 intravenously. On day 19 after immunization, hIRBP-p-specific delayed hypersensitivity (DH) were measured. On day 21 after immunization, animals were sacrificed, and assessed the extent of EAU pathologically. EAU and antigen-specific DH was predominantly suppressed by injection of mature DC cultured with CGRP or TGF-B2 and hIRBP-p. Incidence of EAU on control group was 87% (13 of 15 EAU mice), TGF-B2 culture group was 60% (9 of 15 EAU mice), and CGRP culture group was 28% (5 of 18 EAU mice). On the next experiments, we prepared CGRP gene-transfect-DC by electroporation methods. As the results, CGRP gene-transfect-DC can suppress EAU, and suppress DH spepific for IRBP-p. It was demonstrated that mature DC cultured with CGRP and CGRP gene-transfect-DC play an immunosuppressive role in development of EAU, which were more effective than those cultured with TGF-B2.
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Report
(3 results)
Research Products
(10 results)
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[Journal Article] The role of the ICOS/B7RP-1 T cell costimulatory pathway in murine experimental autoimmune uveoretinitis.2006
Author(s)
Usui Y., Akiba H., Takeuchi M., Kezuka T., Takeuchi A., Hattori T., Okunuki Y., Yamasaki T., Yagita H., Usui M., Okumura K.
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Journal Title
Eur J Immunol 36
Pages: 3071-3081
Description
「研究成果報告書概要(和文)」より
Related Report
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[Journal Article] The role of the ICOS/B7RP-1 T cell costimulatory pathway in murine experimental autoimmune uveoretinitis.2006
Author(s)
Usui Y., Akiba H., Takeuchi M., Kezuka T., Takeuchi A., Hattori T., Okunuki Y., Yamasaki T., Yagita H., Usui M., Okumura K
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Journal Title
Eur J Immunol 36
Pages: 3071-3081
Related Report
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