Melanocytes in psoriasis: convicted culprit or bullied bystander?
Melanocytes in psoriasis: convicted culprit or bullied bystander?
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牛皮癣中的黑色素细胞：被定罪的罪魁祸首还是被欺负的旁观者？
DOI：
10.1111/pcmr.12470
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发表时间：
2016
影响因子：
4.3
通讯作者：
Harris,JohnE
中科院分区：
文献类型：
--
作者：
Strassner,JamesP;Rashighi,Mehdi;Harris,JohnE
最近发表在《实验医学杂志》上的一项研究报告称，黑素细胞可能是牛皮癣患者自身反应性T细胞的靶标。牛皮癣是一种常见的皮肤炎症性疾病，影响着全世界1-3%的人。它表现为界限清晰的鳞状斑块，降低了受影响患者的生活质量（Lowes et al. 2014）。从历史上看，银屑病被认为是一种角化细胞过度增生的疾病，但大多数研究者现在都认为，这种疾病背后的驱动力是免疫信号级联失调，导致银屑病病变的特征性炎症（Lowes et al. 2014）。关于这种疾病是否真的起源于自身免疫，还有一个持续的争论，如果是的话，我们仍然不清楚是什么特定的抗原，更不用说哪种细胞类型，是这种自身免疫反应的目标。牛皮癣的发病机制是由皮肤中的几个免疫群体介导的，许多涉及的炎症途径现在已经很好地描述了。这些途径导致持续的免疫细胞募集、炎症和角质形成细胞的无限制增殖，从而导致增厚的鳞状斑块（Lowes et al. 2014）。在疾病的慢性炎症期，T细胞发挥突出作用，可能产生Th1、Th17或th22特异性细胞因子。其中，IL-23/IL-17/TNF-α轴似乎是疾病发病机制的核心，因为针对该轴进行治疗可以显著改善疾病（Lowes et al. 2014）。传统上，产生IL-17的细胞被认为是αβ T细胞，但最近对人类和小鼠牛皮癣的研究揭示了γδ T细胞作为额外贡献者的新作用（Lowes et al. 2014）。这对疾病中的抗原靶向具有重要意义，因为αβ T细胞识别HLA呈递背景下的特定抗原，而γδ T细胞则不能。
A recent study published in the Journal of Experimental Medicine reports that melanocytes may be targets of autoreactive T cells in psoriasis. Psoriasis is a common inflammatory disease of the skin that affects 1–3% of people worldwide. It presents with well-demarcated, scaly plaques that reduce the quality of life of affected patients (Lowes et al. 2014). Historically, psoriasis was thought to be a disorder of keratinocyte hyperproliferation, but most investigators now agree the driving force behind the disease is a dysregulated immune signaling cascade that results in the characteristically inflamed psoriatic lesions (Lowes et al. 2014). There is an ongoing debate whether the disease is truly autoimmune in origin, and if it is, it remains unclear what specific antigens, let alone which cell types, are the targets of this autoimmune response.The pathogenesis of psoriasis is mediated by several immune populations in the skin, and many of the inflammatory pathways involved are now well described. These pathways lead to continued immune cell recruitment, inflammation, and the unrestrained proliferation of keratinocytes, which gives rise to the thickened, scaly plaques (Lowes et al. 2014). In the chronic inflammatory phase of the disease, T cells play a prominent role, which may produce Th1, Th17 or Th22-specific cytokines. Of these, the IL-23/IL-17/TNF-α axis appears to be central to disease pathogenesis, as targeting this axis for treatment results in vast improvement of the disease (Lowes et al. 2014). Classically, IL-17 producing cells were thought to be αβ T cells, but more recent studies of psoriasis in both humans and mice have revealed an emerging role of γδ T cells as additional contributors (Lowes et al. 2014). This has important implications for antigen targeting in the disease, as αβ T cells recognize specific antigens in the context of HLA presentation, while γδ T cells do not.