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

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五种不同的七种跨膜G蛋白偶联受体传递信号，术语d1至d5。次级淋巴组织由交感神经纤维高度支配，交感神经纤维储存高含量的多巴胺。淋巴细胞也会产生多巴胺。在这里，我们研究了淋巴细胞中多巴胺受体的表达和功能。我们发现D3是次级淋巴组织中主要的多巴胺受体亚型，并选择性地由人和小鼠的幼稚CD8^+T细胞表达。多巴胺诱导稳定表达人D3的小鼠L1.2细胞的钙流动和趋化作用。这些反应几乎完全被百日咳毒素(PTX)抑制，表明D3与G蛋白的Gai类偶联。在人和小鼠的幼稚CD8^+T细胞中，多巴胺一直以对PTX和D3拮抗剂敏感的方式选择性地诱导趋化反应。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的协同作用。多巴胺通过激活整合素选择性地诱导初始CD8~+T细胞与纤维连接蛋白和ICAM-1的黏附。小鼠腹腔注射多巴胺，选择性地将幼稚的CD8~+T细胞吸引到腹腔内。用D3拮抗剂U-99194A处理小鼠，选择性地减少了原始CD8^+T细胞进入淋巴结的归巢。总的来说，在人和小鼠体内，幼稚的CD8^+T细胞都选择性地表达D3，而多巴胺在幼稚的CD8^+T细胞通过D3迁移和归巢中起着重要的作用。

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.