IL-6 Regulates Neutrophil Microabscess Formation in IL-17A-Driven Psoriasiform Lesions
IL-6 Regulates Neutrophil Microabscess Formation in IL-17A-Driven Psoriasiform Lesions
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DOI：
10.1038/jid.2013.404
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发表时间：
2014-03-01
影响因子：
6.5
通讯作者：
Waisman, Ari
中科院分区：
文献类型：
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作者：
Croxford, Andrew L.;Karbach, Susanne;Waisman, Ari
缺乏被普遍接受的人类牛皮癣动物模型阻碍了对该疾病发病机制的研究进展。在这里，我们提出了一个模型，在该模型中，转基因IL-17A的表达针对小鼠的皮肤，在将我们的IL-17A(Ind)等位基因与K14-Cre品系杂交后即可实现。K14-IL-17A(ind/+)小鼠总是表现出明显的皮肤炎症，具有人类银屑病的许多特征，包括真皮效应T细胞的渗透，中性粒细胞微脓肿的形成，以及角化过度。IL-17A在皮肤中的表达导致表达IL-6R的中性粒细胞上调粒细胞和迁移到皮肤中。IL-6信号的中和有效地减少了IL-17A过度表达小鼠皮肤中观察到的发病机制，显著减少了表皮中性粒细胞脓肿的形成和表皮增厚。因此，IL-6在IL-17A下游发挥作用，以加重银屑病样皮损中性粒细胞微脓肿的发展。
The lack of a generally accepted animal model for human psoriasis has hindered progress with respect to understanding the pathogenesis of the disease. Here we present a model in which transgenic IL-17A expression is targeted to the skin in mice, achievable after crossing our IL-17A(ind) allele to the K14-Cre strain. K14-IL-17A(ind/+) mice invariably develop an overt skin inflammation bearing many hallmark characteristics of human psoriasis including dermal infiltration of effector T cells, formation of neutrophil nnicroabscesses, and hyperkeratosis. IL-17A expression in the skin results in upregulated granulopoiesis and migration of IL-6R-expressing neutrophils into the skin. Neutralization of IL-6 signaling efficiently reduces the observed pathogenesis in skin of IL-17A-overexpressing mice, with marked reductions in epidermal neutrophil abscess formation and epidermal thickening. Thus, IL-6 functions downstream of IL-17A to exacerbate neutrophil microabscess development in psoriasiform lesions.