Epithelial TRAF6 drives IL-17-mediated psoriatic inflammation
Epithelial TRAF6 drives IL-17-mediated psoriatic inflammation
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DOI：
10.1172/jci.insight.121175
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发表时间：
2018-08-09
期刊：
影响因子：
8
通讯作者：
Kabashima, Kenji
中科院分区：
文献类型：
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作者：
Matsumoto, Reiko;Dainichi, Teruki;Kabashima, Kenji
上皮细胞是抵御外部危险的第一道防线，有助于诱导包括Th17反应在内的获得性免疫。然而，目前尚不清楚特定的上皮性信号通路是否对发展强大的IL-17介导的免疫反应至关重要。在小鼠中，咪喹莫特诱导的银屑病炎症的发展需要角质形成细胞TRAF6。角质形成细胞中TRAF6的条件性缺失消除了咪喹莫特治疗部位的树突状细胞激活、IL-23的产生和γ-Delta T细胞产生的IL-17。相反，半抗原诱导的接触性超敏反应和木瓜酶诱导的IgE产生不受TRAF6丢失的影响。银屑病炎症的消失不仅仅是由于咪喹莫特感觉缺陷，因为皮下注射IL-23恢复了IL-17的产生，但没有在突变动物中重建银屑病的病理。因此，TRAF6是IL-17介导的炎症充分发展所必需的。因此，上皮性TRAF6信号在触发和传播IL-17介导的银屑病炎症中起着重要作用。
Epithelial cells are the first line of defense against external dangers, and contribute to induction of adaptive immunity including Th17 responses. However, it is unclear whether specific epithelial signaling pathways are essential for the development of robust IL-17-mediated immune responses. In mice, the development of psoriatic inflammation induced by imiquimod required keratinocyte TRAF6. Conditional deletion of TRAF6 in keratinocytes abrogated dendritic cell activation, IL-23 production, and IL-17 production by gamma delta T cells at the imiquimod-treated sites. In contrast, hapten-induced contact hypersensitivity and papain-induced IgE production were not affected by loss of TRAF6. Loss of psoriatic inflammation was not solely due to defective imiquimod sensing, as subcutaneous administration of IL-23 restored IL-17 production but did not reconstitute psoriatic pathology in the mutant animals. Thus, TRAF6 was required for the full development of IL-17-mediated inflammation. Therefore, epithelial TRAF6 signaling plays an essential role in both triggering and propagating IL-17-mediated psoriatic inflammation.