Buhl Timo, Sulk Mathias, Nowak Pawel, Buddenkotte Jörg, McDonald Ian, Aubert Jérôme, Carlavan Isabelle, Déret Sophie, Reiniche Pascale, Rivier Michel, Voegel Johannes J, Steinhoff Martin
Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Germany; Charles Institute for Translational Dermatology, University College Dublin, Dublin, Ireland; Department of Dermatology and Surgery, University of California, San Francisco, California, USA.
Department of Dermatology and Surgery, University of California, San Francisco, California, USA; Department of Dermatology, University of Münster, Münster, Germany.
J Invest Dermatol. 2015 Sep;135(9):2198-2208. doi: 10.1038/jid.2015.141. Epub 2015 Apr 7.
Rosacea is a common chronic inflammatory skin disease of unknown etiology. Our knowledge about an involvement of the adaptive immune system is very limited. We performed detailed transcriptome analysis, quantitative real-time reverse-transcriptase-PCR, and quantitative immunohistochemistry on facial biopsies of rosacea patients, classified according to their clinical subtype. As controls, we used samples from patients with facial lupus erythematosus and healthy controls. Our study shows significant activation of the immune system in all subtypes of rosacea, characterizing erythematotelangiectatic rosacea (ETR) already as a disease with significant influx of proinflammatory cells. The T-cell response is dominated by Th1/Th17-polarized immune cells, as demonstrated by significant upregulation of IFN-γ or IL-17, for example. Chemokine expression patterns support a Th1/Th17 polarization profile of the T-cell response. Macrophages and mast cells are increased in all three subtypes of rosacea, whereas neutrophils reach a maximum in papulopustular rosacea. Our studies also provide evidence for the activation of plasma cells with significant antibody production already in ETR, followed by a crescendo pattern toward phymatous rosacea. In sum, Th1/Th17 polarized inflammation and macrophage infiltration are an underestimated hallmark in all subtypes of rosacea. Therapies directly targeting the Th1/Th17 pathway are promising candidates in the future treatment of this skin disease.
酒渣鼻是一种病因不明的常见慢性炎症性皮肤病。我们对适应性免疫系统参与其中的了解非常有限。我们对酒渣鼻患者的面部活检组织进行了详细的转录组分析、定量实时逆转录聚合酶链反应和定量免疫组织化学分析，并根据临床亚型进行了分类。作为对照，我们使用了面部红斑狼疮患者的样本和健康对照者的样本。我们的研究表明，在所有酒渣鼻亚型中免疫系统均有显著激活，这表明红斑毛细血管扩张型酒渣鼻（ETR）已是一种有大量促炎细胞流入的疾病。例如，通过IFN-γ或IL-17的显著上调证明，T细胞反应以Th1/Th17极化的免疫细胞为主导。趋化因子表达模式支持T细胞反应的Th1/Th17极化特征。在所有三种酒渣鼻亚型中，巨噬细胞和肥大细胞均增多，而中性粒细胞在丘疹脓疱型酒渣鼻中达到最多。我们的研究还提供了证据，表明在ETR中浆细胞已被激活并产生大量抗体，随后向鼻赘型酒渣鼻呈渐进性模式发展。总之，Th1/Th17极化炎症和巨噬细胞浸润是所有酒渣鼻亚型中一个被低估的特征。直接靶向Th1/Th17途径的疗法有望成为未来治疗这种皮肤病的候选方法。
