2012 Fiscal Year Final Research Report
Studies on the Cell Kinetics of Cardiac Dendritic Cell
| Project/Area Number |
22590812
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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 |
Circulatory organs internal medicine
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| Research Institution | Kitasato University |
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Principal Investigator |
IZUMI Tohru 北里大学, 医学部, 名誉教授 (80143775)
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| Project Period (FY) |
2010 – 2012
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| Keywords | 心臓樹状細胞 / 自己免疫性心筋炎 / ミオシン反応性 T 細胞 / GFP / Th17T 細胞 / Cylindromatosis(CYLD) / Interferon regulatory factor(IRF)-3 |
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| Research Abstract |
To clarify dynamic mechanism of cardiac dendritic cell (DC) is the present purpose. Firstly, I established a novel GFP labeled T cell line specific reactive to cardiac myosin (CMT) using CM2 peptide, and analyzed DC activationby the transfer experiment. As a result, persistence of autoimmune myocarditis and change ofT cell subsets were seen. The GFP-CMT infiltrated into the myocardium directly and induced inflammation. In addition, Th17 T cells appeared in vicinity of the lesions followingafter disappearance of GFP-CMT. This phenomenon was an alternation of T-cell. The DC played an important role in the process. For DC cell kinetics, I investigated the transfer myocarditis in GFP overexpressed rat employing non GFP-labeled CMT, and tried to detect GFP-positive DC. Then, I isolated GFP-negative CD3-positive cells and tested them by Flowcytometry. However, I consumed much time to create their chimera models, and so failed to obtain sufficient results. IL-23/27 balance, Th17 immunity, GFP-positive DC mobilization and its TLR signaling emerged as challengeable tasks. On the other hand, Cylindromatosis (CYLD) is an activator of natural immunity and an inhibitor of NF-κB. Expression of this CYLD has been still unclear. In the present search on activated macrophage, it is suggested that Interferon regulatory factor (IRF)-3 is extensively involved in its expression. From a systematic analysis, to provoke myocarditis, to prolong it andto fall into fulminant type, this signal seems to be essential. Currently, DC kinetics in this signaling becomes a new theme.
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