Neutrophil exosomes enhance the skin autoinflammation in generalized pustular psoriasis via activating keratinocytes
Neutrophil exosomes enhance the skin autoinflammation in generalized pustular psoriasis via activating keratinocytes
复制标题
中性粒细胞外泌体通过激活角质形成细胞增强全身性脓疱型银屑病的皮肤自身炎症。
DOI：
10.1096/fj.201802090rr
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发表时间：
2019-06-01
期刊：
影响因子：
4.8
通讯作者：
Wang, Gang
中科院分区：
文献类型：
--
作者：
Shao, Shuai;Fang, Hui;Wang, Gang
泛发性脓疱性牛皮癣(GPP)是一种罕见的严重炎症性皮肤病，可危及生命。在一些病例中发现了基因突变，但其免疫机制在很大程度上尚不清楚。在这里，我们观察到GPP患者的中性粒细胞/淋巴细胞比率高于健康对照组，并在有效治疗后下降。从GPP患者分离的中性粒细胞可诱导角质形成细胞表达IL-1β、IL-36G、IL-18、肿瘤坏死因子-α和C-X-C基序趋化因子配体等炎症基因。此外，GPP患者的中性粒细胞比对照组分泌更多的外切体，并被角质形成细胞迅速内化，通过激活NF-kappa B和MAPK信号通路增加这些炎性分子的表达。中性粒细胞外体的蛋白质组学图谱进一步确定了功能蛋白，并确定了Ofactomedin 4是介导GPP自身免疫性炎症反应的关键差异表达蛋白。这些结果表明，中性粒细胞外体对角质形成细胞具有免疫调节作用，它调节GPP中免疫细胞的迁移和自身炎症。-邵山，方，H，张杰，江明，薛，K，马，J，张，J，雷，J，张，Y.，李，B.，袁，X.，Dang，E.，Wang，G.中性粒细胞外体通过激活角质形成细胞增强泛发性脓疱性银屑病皮肤自身炎症。
Generalized pustular psoriasis (GPP) is a rare and severe inflammatory skin disease that can be life-threatening. Gene mutations are found in some cases, but its immune pathogenesis is largely unknown. Here, we observed that the neutrophil:lymphocyte ratio in patients with GPP was higher than that in healthy controls and decreased after effective treatment. Neutrophils isolated from patients with GPP induced higher expressions of inflammatory genes including IL-1 beta, IL-36G, IL-18, TNF-alpha, and C-X-C motif chemokine ligands in keratinocytes than normal neutrophils did. Moreover, neutrophils from patients with GPP secreted more exosomes than controls, which were then rapidly internalized by keratinocytes, increasing the expression of these inflammatory molecules via activating NF-kappa B and MAPK signaling pathways. The proteomic profiles in neutrophil exosomes further characterized functional proteins and identified olfactomedin 4 as the critical differentially expressed protein that mediates the autoimmune inflammatory responses of GPP. These results demonstrate that neutrophil exosomes have an immune-regulatory effect on keratinocytes, which modulates immune cell migration and autoinflammation in GPP.-Shao, S., Fang, H., Zhang, J., Jiang, M., Xue, K., Ma, J., Zhang, J., Lei, J., Zhang, Y., Li, B., Yuan, X., Dang, E., Wang, G. Neutrophil exosomes enhance the skin autoinflammation in generalized pustular psoriasis via activating keratinocytes.