The serotonin receptor 5-HT7R regulates the morphology and migratory properties of dendritic cells
The serotonin receptor 5-HT7R regulates the morphology and migratory properties of dendritic cells
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DOI：
10.1242/jcs.167999
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发表时间：
2015-08-01
影响因子：
4
通讯作者：
Ponimaskin, Evgeni
中科院分区：
文献类型：
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作者：
Holst, Katrin;Guseva, Daria;Ponimaskin, Evgeni
树突状细胞是有效的抗原呈递细胞，具有在炎症时启动适应性免疫反应的独特能力。炎症过程通常与血清素产生增加有关，血清素通过激活特定受体发挥作用。然而，人们对血清素受体在调节树突状细胞功能中的功能作用知之甚少。在这里，我们证明了成熟时树突状细胞中血清素受体 5-HT7 (5-HT7R) 及其下游效应器 Cdc42 的表达上调。尽管树突状细胞成熟独立于 5-HT7R，但受体刺激通过 Cdc42 介导的信号传导影响树突状细胞形态。此外，5-HT7R 的基础活性是趋化因子受体 CCR7 正确表达所必需的，CCR7 是控制树突状细胞迁移的关键因素。与此一致的是，我们观察到 5-HT7R 通过调节树突状细胞的方向性和迁移速度来增强体外树突状细胞的趋化运动。因此，药理学受体抑制后，鼠结肠外植体中树突状细胞的迁移被消除。我们的结果表明，5-HT7R-Cdc42介导的信号传导在树突状细胞形态和运动的调节中起着至关重要的作用，这表明5-HT7R可能成为治疗多种炎症和免疫性疾病的新靶点。
Dendritic cells are potent antigen-presenting cells endowed with the unique ability to initiate adaptive immune responses upon inflammation. Inflammatory processes are often associated with an increased production of serotonin, which operates by activating specific receptors. However, the functional role of serotonin receptors in regulation of dendritic cell functions is poorly understood. Here, we demonstrate that expression of serotonin receptor 5-HT7 (5-HT7R) as well as its downstream effector Cdc42 is upregulated in dendritic cells upon maturation. Although dendritic cell maturation was independent of 5-HT7R, receptor stimulation affected dendritic cell morphology through Cdc42-mediated signaling. In addition, basal activity of 5-HT7R was required for the proper expression of the chemokine receptor CCR7, which is a key factor that controls dendritic cell migration. Consistent with this, we observed that 5-HT7R enhances chemotactic motility of dendritic cells in vitro by modulating their directionality and migration velocity. Accordingly, migration of dendritic cells in murine colon explants was abolished after pharmacological receptor inhibition. Our results indicate that there is a crucial role for 5-HT7R-Cdc42-mediated signaling in the regulation of dendritic cell morphology and motility, suggesting that 5-HT7R could be a new target for treatment of a variety of inflammatory and immune disorders.