Roosterman Dirk, Goerge Tobias, Schneider Stefan W, Bunnett Nigel W, Steinhoff Martin
Department of Dermatology, IZKF Münster, Germany.
Physiol Rev. 2006 Oct;86(4):1309-79. doi: 10.1152/physrev.00026.2005.
This review focuses on the role of the peripheral nervous system in cutaneous biology and disease. During the last few years, a modern concept of an interactive network between cutaneous nerves, the neuroendocrine axis, and the immune system has been established. We learned that neurocutaneous interactions influence a variety of physiological and pathophysiological functions, including cell growth, immunity, inflammation, pruritus, and wound healing. This interaction is mediated by primary afferent as well as autonomic nerves, which release neuromediators and activate specific receptors on many target cells in the skin. A dense network of sensory nerves releases neuropeptides, thereby modulating inflammation, cell growth, and the immune responses in the skin. Neurotrophic factors, in addition to regulating nerve growth, participate in many properties of skin function. The skin expresses a variety of neurohormone receptors coupled to heterotrimeric G proteins that are tightly involved in skin homeostasis and inflammation. This neurohormone-receptor interaction is modulated by endopeptidases, which are able to terminate neuropeptide-induced inflammatory or immune responses. Neuronal proteinase-activated receptors or transient receptor potential ion channels are recently described receptors that may have been important in regulating neurogenic inflammation, pain, and pruritus. Together, a close multidirectional interaction between neuromediators, high-affinity receptors, and regulatory proteases is critically involved to maintain tissue integrity and regulate inflammatory responses in the skin. A deeper understanding of cutaneous neuroimmunoendocrinology may help to develop new strategies for the treatment of several skin diseases.
本综述聚焦于外周神经系统在皮肤生物学及疾病中的作用。在过去几年间，已建立起一种关于皮肤神经、神经内分泌轴及免疫系统之间交互网络的现代概念。我们了解到神经皮肤相互作用会影响多种生理和病理生理功能，包括细胞生长、免疫、炎症、瘙痒及伤口愈合。这种相互作用由初级传入神经以及自主神经介导，它们释放神经介质并激活皮肤中许多靶细胞上的特定受体。密集的感觉神经网络释放神经肽，从而调节皮肤中的炎症、细胞生长及免疫反应。神经营养因子除了调节神经生长外，还参与皮肤功能的许多特性。皮肤表达多种与异源三聚体G蛋白偶联的神经激素受体，这些受体紧密参与皮肤稳态和炎症过程。这种神经激素 - 受体相互作用受到内肽酶的调节，内肽酶能够终止神经肽诱导的炎症或免疫反应。神经元蛋白酶激活受体或瞬时受体电位离子通道是最近描述的受体，它们可能在调节神经源性炎症、疼痛和瘙痒方面发挥重要作用。总之，神经介质、高亲和力受体和调节蛋白酶之间紧密的多向相互作用对于维持组织完整性和调节皮肤炎症反应至关重要。对皮肤神经免疫内分泌学的更深入理解可能有助于开发治疗多种皮肤病的新策略。
