Neutrophil extracellular trap formation is increased in psoriasis and induces human β-defensin-2 production in epidermal keratinocytes.
Neutrophil extracellular trap formation is increased in psoriasis and induces human β-defensin-2 production in epidermal keratinocytes.
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DOI：
10.1038/srep31119
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发表时间：
2016-08-05
影响因子：
4.6
通讯作者：
Lan CC
中科院分区：
文献类型：
--
作者：
Hu SC;Yu HS;Yen FL;Lin CL;Chen GS;Lan CC
神经元细胞外陷阱（NET）已涉及某些免疫介导的疾病的发展，但其在银屑病中的作用尚未明确界定。人β-防御素-2（HBD-2）是银屑病表皮中高表达的重要抗菌肽。我们评估了NET的量是否在银屑病中增加，并确定了NET对表皮角质形成细胞中HBD-2产生的影响。使用荧光显微镜，我们发现银屑病患者（n = 48）与健康对照组（n = 48）和湿疹患者（n = 35）相比，其外周血中NETotic细胞的量更高。在对照组中性粒细胞中，银屑病血清诱导NET形成的能力增加，但NET降解能力正常。外周血中NET的量与银屑病疾病的严重程度相关。在大多数（18/20）银屑病皮肤标本中也观察到NETosis。此外，NETs诱导角质形成细胞中HBD-2 mRNA和蛋白的产生，免疫组化分析证实了HBD-2在银屑病皮损皮肤中的强表达。总之，银屑病患者外周血和皮损中NET形成增加，并与疾病严重程度相关。此外，NET诱导的HBD-2产生可能为降低银屑病斑块对微生物感染的易感性提供了一种新的机制。
Neutrophil extracellular traps (NETs) have been implicated in the development of certain immune-mediated diseases, but their role in psoriasis has not been clearly defined. Human β-defensin-2 (HBD-2) is an important antimicrobial peptide overexpressed in psoriasis epidermis. We evaluated whether the amount of NETs is increased in psoriasis and determined the effect of NETs on HBD-2 production in epidermal keratinocytes. Using fluorescent microscopy, we found that patients with psoriasis (n = 48) had higher amount of NETotic cells in their peripheral blood compared to healthy controls (n = 48) and patients with eczema (n = 35). Psoriasis sera showed increased ability to induce NET formation in control neutrophils but normal NET degradation ability. The amount of NETs in the peripheral blood correlated with psoriasis disease severity. NETosis was also observed in the majority (18 of 20) of psoriasis skin specimens. Furthermore, NETs induced HBD-2 mRNA and protein production in keratinocytes, and immunohistochemical analysis confirmed strong expression of HBD-2 in psoriasis lesional skin. In summary, NET formation is increased in peripheral blood and lesional skin of psoriasis patients and correlates with disease severity. Additionally, NET-induced HBD-2 production may provide a novel mechanism for the decreased susceptibility of psoriasis plaques to microbial infections.