2007 Fiscal Year Final Research Report Summary
Possible new factors that regulate the homing specificity of immune cells
| Project/Area Number |
17390147
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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 | Tokushima Bunri University |
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Principal Investigator |
IWATA Makoto Tokushima Bunri University, Faculty of Pharmaceutical Sciences at Kagawa Campus, Professor (50160122)
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| Co-Investigator(Kenkyū-buntansha) |
SONG Si-young Tokushima Bunri University, Institute of Neuroscience, Professor (00399693)
OHOKA Yoshiharu Tokushima Bunri University, 香川薬学部, Associate Professor (60303971)
TAKEUCHI Hajime Tokushima Bunri University, 香川薬学部, Assistant Professor (00421298)
YOKOTA Aya Tokushima Bunri University, 香川薬学部, Assistant Professor (30446075)
YOKOYAMA Minesuke Niigata University, Brain Research Institute, Professor (40090930)
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| Project Period (FY) |
2005 – 2007
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| Keywords | Lymphocyte / Homing specificity / Imprint / Retinoic acid / Vitamin A / Retinal dehydrogenase / Vitamin D / GM-CSF |
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| Research Abstract |
To exert the immunological functions efficiently, lymphocytes need to migrate into the specific sites where antigen has invaded. Lymphocytes that encountered antigen in gut-related lymphoid organs prefer to migrate into small-intestinal tissues. There are dendritic cells (DC) capable of producing retinoic acid (RA) from vitamin A in the gut. We found that these DC imprint T cells with small intestine-homing specificity by giving RA to T cells during antigen presentation. In this project, we searched for the factor that regulates other homing specificity or disrupts the homing specificity, and analyzed its action mechanism to develop a new basis for treating and preventing diseases through the regulation of lymphocyte homing. We found that the vitamin D metabolite, lα, 25-dihydroxyvitamin D_3 (VitD3), enhanced the expression of a part of skin-specific homing receptors, and suppressed the RA-dependent expression of small intestine-specific homing receptors, using in vitro-experimental sy
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stems and an in vivo-cell transfer experimental system. It was recently proposed that VitD3 imprints skin-homing specificity on human T cells. However, the VitD3 role on the skin-specific homing appeared to be limited. We found that glucocorticoids suppressed the expression of a part of homing receptors, but that other known nuclear-receptor ligands exerted little effect on the homing-receptor expression. Some environmental chemicals enhanced the RA effect on the homing-receptor, expression, and thus they might cause to disrupt tissue-specific lymphocyte homing. We also established a method to assess retinal dehydrogenase (RALDH) activity in individual cells, and could identify the specific population of DC capable of producing RA. We then found that GM-CSF is a major physiological factor that induces the expression of RALDH in DC. IL-4 and RA itself enhanced or assisted the GM-CSF-induced RALDH expression. Stimulation by commensal bacteria might also participate in inducing the RALDH expression in DC. Since it was recently reported that RA also contribute to the induction and differentiation of inducible Foxp3^+ regulatory T cells (iTreg), we examined a possibility that the regulation of RALDH expression in DC might regulate the induction of iTreg, and we could verify it. Furthermore, we found that RA also imprints B cells, including IgA-producing cells, with small intestine-homing specificity, and that IgA antibody response requires DC expressing both RALDH and TNF-1/inducible-nitric-oxide synthase. Less
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Research Products
(77 results)
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[Presentation] Induction of retinal dehydrogenase(RALDH) required for imprinting gut-homing specificity on lymphocytes, in murine dendritic cells.2007
Author(s)
YOKOTA, A., TAKEUCHI, H., OHOKA, Y., SONG, S.-Y., IWATA, M.
Organizer
The 37th Annual Meeting of the Japanese Society for Immunology
Place of Presentation
at Tokyo
Year and Date
2007-11-20
Description
「研究成果報告書概要(欧文)」より
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