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Role of CCL19/ 21 chemokine in the development of experimental autoimmune encephalomyelitis

CCL19/21趋化因子在实验性自身免疫性脑脊髓炎发生中的作用

基本信息

批准号：
17590900
负责人：
KAKIUCHI Terutaka
金额：
$ 2.24万
依托单位：
Toho University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590900/
关键词：
plt mouse CCL21 chemokine CCL19 chemokine IL-17 IL-23 T cell EAE multiple sclerosis

项目摘要

Experimental autoimmune encephalomyelitis (EAE) in mouse is a model of multiple sclerosis. We have investigated the role of CCL21/19 chemokine in the regulation of immune response, using mutant mouse lacking the expression of CCL19/21 (paucity of lymph node T cells: plt) which was found in our laboratory. During investigation, we found that these mutant mice are resistant to the induction of EAE. In the present study, we analyzed the mechanisms for the resistance, and obtained following results.(1) Recently, it has been established that Th-17 cells other than Th-1 cells are responsible to the development of EAE. In plt mice Th-17 cells did not differentiated after immunization with myelin-oligodendrocyte glycoprotein (MOG) 35-55 peptide in CFA, which induced Th-17 cells and EAE in wild type (WT) mice.(2) IL-6, TGF-beta and IL-23 are required for the production of IL-17. When draining lymph node cells were incubated, IL-6 and TGF-beta were detected in the culture supernatant of the lymph node cells from plt mice similarly to that from WT mice, IL-23 was very low.(3) Addition of IL-23 to the culture of CD4+ T cells from draining lymph nodes of plt mice induced production of IL-17.(4) The addition of CCL21 chemokine to the culture of CD4+ T cells from draining lymph nodes of plt mice was not effective to the induction of IL-17 production.(5) Purified CD11c+ dendritic cells produced IL-23 in the presence of CCL21.(6) CD11c+ dendritic cells from CCR7-deficient mice did not produce IL-23 even when CCL21 was present.These results suggested that in plt mice Th-17 cells were not induced due to the lack of IL-23, which was resulted from the deficient stimulation of CCR7 in the mice lacking the expression of CCL21/19 chemokine.Our next project is developing the procedures to treat EAE by manipulating IL-23 or CCL21/19 chemokine.

实验性自身免疫性脑脊髓炎（EAE）是一种多发性硬化的动物模型。我们已经研究了CCL 21/19趋化因子在免疫应答调节中的作用，使用我们实验室发现的缺乏CCL 19/21表达的突变小鼠（缺乏淋巴结T细胞：plt）。在研究过程中，我们发现这些突变小鼠对EAE的诱导有抵抗力。本研究通过对耐药机制的分析，得出以下结论：(1)最近，已经确定Th-17细胞而不是Th-1细胞负责EAE的发展。在plt小鼠中，用CFA中的髓鞘-少突胶质细胞糖蛋白（MOG）35-55肽免疫后，Th-17细胞没有分化，这诱导了野生型（WT）小鼠中的Th-17细胞和EAE。(2)IL-6、TGF-β和IL-23是产生IL-17所必需的。当培养引流淋巴结细胞时，在plt小鼠淋巴结细胞的培养上清液中检测到IL-6和TGF-β，与WT小鼠相似，IL-23非常低。(3)将IL-23加入到来自plt小鼠引流淋巴结的CD 4 + T细胞的培养物中诱导IL-17的产生。(4)在plt小鼠引流淋巴结的CD_4 ~+ T细胞培养中加入CCL_（21）趋化因子对诱导IL-17的产生没有效果。(5)纯化的CD 11 c+树突状细胞在CCL 21存在下产生IL-23。(6)这些结果表明，在plt小鼠中，Th-17细胞由于缺乏IL-23而未被诱导，这是由于CCL 21/19趋化因子缺乏的小鼠中CCR 7的刺激不足所致。我们的下一个项目是开发通过操纵IL-10来治疗EAE的方法。23或CCL 21/19趋化因子。

项目成果

期刊论文数量（15）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Loss of dendritic cell migration and impaired resistance to Leishmania donovani infection in mice deficient in CCL19 and CCL21

DOI：
10.4049/jimmunol.176.9.5486
发表时间：
2006-05-01
期刊：
JOURNAL OF IMMUNOLOGY
影响因子：
4.4
作者：
Ato, Manabu;Maroof, Asher;Kaye, Paul M.
通讯作者：
Kaye, Paul M.

CXCL9 antagonism further extends prolonged cardiac allograft survival in CCL19/CCL2l-deficient mice.

CXCL9 拮抗作用进一步延长了 CCL19/CCL2l 缺陷小鼠的同种异体心脏移植存活时间。

DOI：
发表时间：
2005
期刊：
Am J Transplant 5・9
影响因子：
0
作者：
Colvin BL;Wang Z;Nakano H;Wu W;Kakiuchi T;Fairchild RL;Thomson AW.
通讯作者：
Thomson AW.

Role of CCL21 and CCL19 in allergic inflammation in the ovalbumin-specific murine asthmatic model.

DOI：
10.1016/j.jaci.2006.01.009
发表时间：
2006-05
期刊：
The Journal of allergy and clinical immunology
影响因子：
0
作者：
Naomi Yamashita;H. Tashimo;Y. Matsuo;H. Ishida;K. Yoshiura;Katsuaki Sato;N. Yamashita;T. Kakiuchi;K. Ohta
通讯作者：
Naomi Yamashita;H. Tashimo;Y. Matsuo;H. Ishida;K. Yoshiura;Katsuaki Sato;N. Yamashita;T. Kakiuchi;K. Ohta

Immunology handbook

免疫学手册