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The role of chemokine system on the metastasis to the lymph node in oral cancer and its clinical application.

趋化因子系统在口腔癌淋巴结转移中的作用及其临床应用

基本信息

批准号：
17592071
负责人：
KATOU Fuminori
金额：
$ 1.22万
依托单位：
Hamamatsu University School of Medicine
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-17592071/
关键词：
naive CD8+ T cells homing lymph node dopamine receptor D3 口腔癌ケモカイン

项目摘要

The nervous systems affect immune functions by releasing neurohormones and neurotransmitters. A neurotransmitter dopamine signals via five different seven transmembrane G protein-coupled receptors terms D1 to D5. The secondary lymphoid tissues are highly innervated by sympathetic nerve fibers that store dopamine at high contents. Lymphocytes also produce dopamine. Here, we examined expression and function of dopamine receptors in lymphocytes. We found that D3 was the predominant subtype of dopamine receptors in the secondary lymphoid tissues and selectively expressed by naive CD8^+ T cells of both human and mouse. Dopamine induced calcium flux and chemotaxis in mouse L1.2 cells stably expressing human D3. These responses were almost completely inhibited by pertussis toxin (PTX), indicating that D3 was coupled with the Gai class of G proteins. Consistently, dopamine selectively induced chemotactic responses in naive CD8^+ T cells of both human and mouse in a manner sensitive to PTX and D3 antagonists. Dopamine was highly synergistic with CCL19, CCL21, and CXCL12 in induction of chemotaxis in naive CD8^+ T cells. Dopamine selectively induced adhesion of naive CD8^+ T cells to fibronectin and ICAM-1 through activation of integrins. Intraperitoneal injection of mice with dopamine selectively attracted naive CD8^+ T cells into the peritoneal cavity. Treatment of mice with a D3 antagonist U-99194A selectively reduced homing of naive CD8^+ T cells into lymph nodes. Collectively, naive CD8^+ T cells selectively express D3 in both human and mouse, and dopamine plays a significant role in migration and homing of naive CD8^+ T cells via D3.

神经系统通过释放神经激素和神经递质来影响免疫功能。神经递质多巴胺通过5个不同的7个跨膜G蛋白偶联受体D1到D5发出信号。二级淋巴组织受交感神经纤维的高度支配，交感神经纤维储存大量多巴胺。淋巴细胞也产生多巴胺。在这里，我们检测了淋巴细胞中多巴胺受体的表达和功能。我们发现D3是次要淋巴组织中多巴胺受体的主要亚型，并在人和小鼠的幼稚CD8^+ T细胞中选择性表达。多巴胺诱导稳定表达人D3的小鼠L1.2细胞的钙通量和趋化性。这些反应几乎完全被百日咳毒素（PTX）抑制，表明D3与Gai类G蛋白偶联。一致地，多巴胺选择性地诱导人和小鼠的初始CD8^+ T细胞对PTX和D3拮抗剂敏感的趋化反应。多巴胺与CCL19、CCL21和CXCL12在诱导初始CD8^+ T细胞趋化方面具有高度协同作用。多巴胺通过激活整合素选择性诱导幼稚CD8^+ T细胞粘附于纤维连接蛋白和ICAM-1。小鼠腹腔注射多巴胺选择性地吸引幼稚的CD8^+ T细胞进入腹腔。用D3拮抗剂U-99194A治疗小鼠选择性地减少了初始CD8^+ T细胞进入淋巴结的归巢。总的来说，人和小鼠的初始CD8^+ T细胞选择性地表达D3，多巴胺在初始CD8^+ T细胞通过D3迁移和归巢中发挥重要作用。