Streilein J W, Alard P, Niizeki H
Schepens Eye Research Institute, Boston, MA 02114, USA.
Keio J Med. 1999 Mar;48(1):22-7. doi: 10.2302/kjm.48.22.
More than 20 years have passed since the concept that the skin has its own associated immune system was first proposed by Streilein. This proposal was advanced in part on evidence that cutaneous contact hypersensitivity (CH) reactions are closely correlated with Langerhans cells (LC). Recent reports have demonstrated that LC have neural connectivity with cutaneous nerve termini containing calcitonin gene-related peptide (CGRP), suggesting that a link exists between innervation and immune responses in the skin. Here we discuss the neural components which have recently been found to be participants in skin-associated lymphoid tissue (SALT). In part, discovery of a functional link between the nervous system and SALT is based on studies in which cutaneous immunity was impaired by ultraviolet-B radiation (UVR). The deleterious effects of UVR on cutaneous immunity include failed CH induction and promotion of hapten-specific tolerance, effects that are mediated by tumor necrosis factor-alpha and interleukin-10, respectively. The source of these cytokines after UVR appears to be dermal mast cells. Evidence indicates that mast cells are triggered to release these cytokines in response to CGRP, which is released from UVR-damaged cutaneous nerve endings. Moreover, a substance P agonist was able to reverse the deleterious effects of UVR on CH induction, rendering the mice able to develop intense CH. These observations indicate that two cell types not originally included in the SALT concept are critical to the functional integrity of cutaneous immunity: mast cells and cutaneous nerves. We propose that cutaneous nerves dictate whether antigen applied to or arising within skin will lead to sensitivity or tolerance.
自斯特赖林首次提出皮肤有其自身相关免疫系统的概念以来，已经过去了20多年。这一观点的提出部分基于皮肤接触性超敏反应（CH）与朗格汉斯细胞（LC）密切相关的证据。最近的报道表明，LC与含有降钙素基因相关肽（CGRP）的皮肤神经末梢存在神经连接，这表明皮肤的神经支配与免疫反应之间存在联系。在这里，我们讨论最近发现的参与皮肤相关淋巴组织（SALT）的神经成分。部分地，神经系统与SALT之间功能联系的发现是基于紫外线B辐射（UVR）损害皮肤免疫的研究。UVR对皮肤免疫的有害影响包括CH诱导失败和促进半抗原特异性耐受，这些影响分别由肿瘤坏死因子-α和白细胞介素-10介导。UVR后这些细胞因子的来源似乎是真皮肥大细胞。有证据表明，肥大细胞在CGRP的作用下被触发释放这些细胞因子，而CGRP是从UVR损伤的皮肤神经末梢释放的。此外，P物质激动剂能够逆转UVR对CH诱导的有害影响，使小鼠能够产生强烈的CH。这些观察结果表明，两种最初未包含在SALT概念中的细胞类型对皮肤免疫的功能完整性至关重要：肥大细胞和皮肤神经。我们提出，皮肤神经决定了应用于皮肤或在皮肤内产生的抗原是会导致敏感还是耐受。
