Studies on the Cell Kinetics of Cardiac Dendritic Cell

心脏树突状细胞的细胞动力学研究

基本信息

批准号：
22590812
负责人：
IZUMI Tohru
金额：
$ 2.83万
依托单位：
Kitasato University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2010
资助国家：
日本
起止时间：
2010 至 2012
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22590812/
关键词：
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 Myocarditis Dendritic cell T cell CYLD IRF 樹状細胞心筋炎自己免疫 T細胞細胞移注 Tリンパ球

项目摘要

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.

为了阐明心脏树突状细胞（DC）的动态机制是当前的目的。首先，我使用CM2肽建立了一个新型的GFP，标记了T细胞系特异性对心脏肌球蛋白（CMT）的反应性，并通过转移实验分析了DC激活。结果，自身免疫性心肌炎的持久性和T细胞子集的变化。 GFP-CMT直接渗入心肌并诱导注射。此外，GFP-CMT消失后，Th17 T细胞出现在病变附近。这种现象是T细胞的替代方法。 DC在此过程中发挥了重要作用。对于DC细胞动力学，我研究了使用非GFP标记的CMT的GFP过表达的大鼠转移心肌炎，并试图检测GFP阳性DC。然后，我分离了GFP阴性CD3阳性细胞，并通过流循环仪对其进行了测试。但是，我花了很多时间来创建他们的嵌合体模型，因此未能获得足够的结果。 IL-23/27平衡，Th17免疫以及GFP阳性直流动员及其TLR信号传导作为有挑战性的任务出现。另一方面，胞染色体病（CYLD）是天然免疫辅助和NF-κB抑制剂的激活剂。该CYLD的表达尚不清楚。在目前对活化巨噬细胞的搜索中，建议干扰素调节因子（IRF）-3广泛参与其表达。从系统的分析，引起心肌炎，延长其延长并陷入全身类型，该信号似乎是必不可少的。当前，此信号中的DC动力学成为一个新主题。