2007 Fiscal Year Final Research Report Summary
Elucidation of regulation of dendritic cells based on the real functional concept
| Project/Area Number |
18590481
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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 |
Immunology
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| Research Institution | The Institute of Physical and Chemical Research |
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Principal Investigator |
FUJII Shin-ichiro The Institute of Physical and Chemical Research, Research Unit for Cellular Immunotherapy, Unit Leader (10392094)
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| Project Period (FY) |
2006 – 2007
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| Keywords | dendritic cells / indoleamine 2.3-dioxyannase(IDO) / adaotive immunity / immunotolerance / metabolite |
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| Research Abstract |
It is well known that dendritic cells (DCs) play a role in the immune defense against tumor or infection. Howeve4 lots of mature or semi-mature DCs led by several kinds of cytokines have been identified. Therefore, to establish the precise concept of functional maturation of dendritic cell (DC) is required. In the current study under the granting, we have had two goals for this topic, establishment of "functional maturation of DCs".
(I) Establishment of therapeutic tumor models by induction of functional DCs in situ: lb aim this, we used the cellular adjuvant by NKT cells. We found that administration of NKT cell ligand-loaded tumor cells led to innate immunity as well as adaptive immunity in vivo through DC maturation. When we analyzed DC in situ, we found that these DCs capture the debris of tumor cells and underwent the maturation. In contrast, when we used CD40 deficient mice, this immunity was abrogated. Thus, functional maturation in situ was induced by the CD40 ligation of DCs, and the functional maturation drives to the strong antitumor effect against tumor cells.
(II) To elucidate the functional maturation, we have focused on the two molecules, that is arginase and indoleamine 2, 3-dioxygenase (IDO). Both have been known as suppressive factors for T cell immunity. Howeve4 from our data arginase inhibitor does not work for DC stimulation for T cells in allogeneic mixed lymphocyte assay (MLR) assays. On the other hand, IDO was enhanced in mature DCs led by TNF-α or IFN-γ or both. Such inflammatory cytokine-induced, mature DCs did not reveal the strong MLR Although PGE2 alone did not enhance IDO, PGE2 together with TNF-α or WN-γ enhanced IDO from DCs. In spite of them, this combination may lead the strong MLR These findings suggest that expression of MO can be enhanced under the condition from environment even in the presence of strong maturation stimuli and we need to pay attention for the maturation stimuli in terms of metabolite from DCs.
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Research Products
(12 results)
