Peters Eva Milena Johanne, Michenko Anna, Kupfer Jörg, Kummer Wolfgang, Wiegand Silke, Niemeier Volker, Potekaev Nikolay, Lvov Andrey, Gieler Uwe
Psychoneuroimmunology Laboratory, Joint appointment a) Center for Internal Medicine and Dermatology, Universitätsmedizin-Charité, Berlin, and b) Department of Psychosomatic Medicine, Justus-Liebig-University, Giessen, Germany.
Psychoneuroimmunology Laboratory, Joint appointment a) Center for Internal Medicine and Dermatology, Universitätsmedizin-Charité, Berlin, and b) Department of Psychosomatic Medicine, Justus-Liebig-University, Giessen, Germany; Department of Dermatology, I. M. Sechenov Moscow Medical University, Moscow, Russia.
PLoS One. 2014 Dec 2;9(12):e113552. doi: 10.1371/journal.pone.0113552. eCollection 2014.
In mouse models for atopic dermatitis (AD) hypothalamus pituitary adrenal axis (HPA) dysfunction and neuropeptide-dependent neurogenic inflammation explain stress-aggravated flares to some extent. Lately, cholinergic signaling has emerged as a link between innate and adaptive immunity as well as stress responses in chronic inflammatory diseases. Here we aim to determine in humans the impact of acute stress on neuro-immune interaction as well as on the non-neuronal cholinergic system (NNCS).
Skin biopsies were obtained from 22 individuals (AD patients and matched healthy control subjects) before and after the Trier social stress test (TSST). To assess neuro-immune interaction, nerve fiber (NF)-density, NF-mast cell contacts and mast cell activation were determined by immunohistomorphometry. To evaluate NNCS effects, expression of secreted mammal Ly-6/urokinase-type plasminogen activator receptor-related protein (SLURP) 1 and 2 (endogenous nicotinic acetylcholine receptor ligands) and their main corresponding receptors were assessed by quantitative RT-PCR.
With respect to neuro-immune interaction we found higher numbers of NGF+ dermal NF in lesional compared to non-lesional AD but lower numbers of Gap43+ growing NF at baseline. Mast cell-NF contacts correlated with SCORAD and itch in lesional skin. With respect to the NNCS, nicotinic acetylcholine receptor α7 (α7nAChR) mRNA was significantly lower in lesional AD skin at baseline. After TSST, PGP 9.5+ NF numbers dropped in lesional AD as did their contacts with mast cells. NGF+ NF now correlated with SCORAD and mast cell-NF contacts with itch in non-lesional skin. At the same time, SLURP-2 levels increased in lesional AD skin.
In humans chronic inflammatory and highly acute psycho-emotional stress interact to modulate cutaneous neuro-immune communication and NNCS marker expression. These findings may have consequences for understanding and treatment of chronic inflammatory diseases in the future.
在特应性皮炎（AD）小鼠模型中，下丘脑-垂体-肾上腺轴（HPA）功能障碍和神经肽依赖性神经源性炎症在一定程度上解释了应激加重的皮疹发作。最近，胆碱能信号已成为慢性炎症性疾病中固有免疫和适应性免疫以及应激反应之间的联系。在此，我们旨在确定在人类中急性应激对神经免疫相互作用以及非神经元胆碱能系统（NNCS）的影响。
在特里尔社会应激测试（TSST）前后，从22名个体（AD患者和匹配的健康对照受试者）获取皮肤活检样本。为评估神经免疫相互作用，通过免疫组织形态计量学确定神经纤维（NF）密度、NF-肥大细胞接触和肥大细胞活化情况。为评估NNCS的作用，通过定量逆转录聚合酶链反应（RT-PCR）评估分泌型哺乳动物Ly-6/尿激酶型纤溶酶原激活物受体相关蛋白（SLURP）1和2（内源性烟碱型乙酰胆碱受体配体）及其主要相应受体的表达。
关于神经免疫相互作用，我们发现与非皮损性AD相比，皮损性AD中NGF+真皮NF数量更多，但基线时Gap43+生长中的NF数量更少。肥大细胞-NF接触与皮损性皮肤中的SCORAD和瘙痒相关。关于NNCS，基线时皮损性AD皮肤中烟碱型乙酰胆碱受体α7（α7nAChR）mRNA显著降低。TSST后，皮损性AD中PGP 9.5+ NF数量及其与肥大细胞的接触减少。现在，NGF+ NF与非皮损性皮肤中的SCORAD以及肥大细胞-NF接触与瘙痒相关。同时，皮损性AD皮肤中SLURP-2水平升高。
在人类中，慢性炎症和高度急性的心理情绪应激相互作用，调节皮肤神经免疫通讯和NNCS标志物表达。这些发现可能对未来慢性炎症性疾病的理解和治疗产生影响。
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