Immunological role of neuronal receptor vanilloid receptor 1 expressed on dendritic cells

Immunological role of neuronal receptor vanilloid receptor 1 expressed on dendritic cells
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DOI:
10.1073/pnas.0407780102
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发表时间:
2005-04-05
影响因子:
11.1
通讯作者:
Srivastava, P
Srivastava, P
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Basu, S;Srivastava, P

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辣椒素(CP)是辣椒中的辛辣成分,作用于感觉神经元,传递疼痛的感觉。在背根和三叉神经节的伤害性神经元中,CP受体香草酸受体1(VR1)高表达。我们在这里证明,树突状细胞(DC)是脊椎动物免疫系统的一种关键细胞类型,表达VR1。通过上调抗原递呈分子和共刺激分子的表达,VR1与未成熟的DC结合,如用CP处理,可导致DC成熟。这种效应存在于VR1(+/+)小鼠的DC中,但不存在于VR1(-/-)小鼠的DC中。在VR1(+/+)小鼠中,这种作用被VR1拮抗剂卡萨西平抑制。此外,皮内注射CP会导致VR1(+/+)小鼠的DC迁移到引流淋巴结,但不会导致VR1(-/-)小鼠的DC迁移到引流淋巴结。这些数据显示了神经活性配体对免疫功能的中心方面的强大影响,以及神经和免疫功能之间的机制路径的共性。
Capsaicin (CP), the pungent component of chili pepper, acts on sensory neurons to convey the sensation of pain. The CP receptor, vanilloid receptor 1 (VR1), has been shown to be highly expressed by nociceptive neurons in dorsal root and trigeminal ganglia. We demonstrate here that the dendritic cell (DC), a key cell type of the vertebrate immune system, expresses VR1. Engagement of VR1 on immature DCs such as by treatment with CP leads to maturation of DCs as measured by up-regulation of antigen-presenting and costimulatory molecules. This effect is present in DCs of VR1(+/+) but not VR1(-/-) mice. In VR1(+/+) mice, this effect is inhibited by the VR1 antagonist capsazepine. Further, intradermal administration of CP leads to migration of DCs to the draining lymph nodes in VR1(+/+) but not VR1(-/-) mice. These data demonstrate a powerful influence of a neuroactive ligand on a central aspect of immune function and a commonality of mechanistic pathways between neural and immune functions.