Autoimmune skin inflammation is dependent on plasmacytoid dendritic cell activation by nucleic acids via TLR7 and TLR9.
Autoimmune skin inflammation is dependent on plasmacytoid dendritic cell activation by nucleic acids via TLR7 and TLR9.
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DOI：
10.1084/jem.20101048
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发表时间：
2010-12-20
期刊：
影响因子：
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通讯作者：
Barrat FJ
中科院分区：
文献类型：
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作者：
Guiducci C;Tripodo C;Gong M;Sangaletti S;Colombo MP;Coffman RL;Barrat FJ
易患狼疮的小鼠会对皮肤损伤产生慢性炎症反应，这取决于 I 型干扰素、TLR7 和 TLR9 的产生。表达 TLR7 和 TLR9 的细胞对内源性 DNA 和 RNA 的识别是系统性红斑狼疮发病机制的重要因素，并且已被认为与皮肤狼疮和一组称为界面皮炎的相关炎症性皮肤病有关。我们使用胶带剥离技术开发了 TLR7 和 TLR9 依赖性皮肤炎症小鼠模型。在正常小鼠中，这导致快速但短暂的炎症细胞浸润，同时诱导浆细胞样树突状细胞（PDC）产生 I 型干扰素，并由中性粒细胞释放细胞外陷阱和促炎细胞因子。在 MyD88 缺陷小鼠和用 TLR7 和 TLR9 双功能抑制剂治疗的小鼠中，这些反应明显减弱。相比之下，在易患狼疮的 (NZBxNZW)F1 小鼠中，胶带剥离诱导慢性病变的发展，其特征是持续的 I 型 IFN 基因特征和皮肤狼疮的许多临床和组织学特征。损伤前去除 PDC 可防止皮肤损伤的发展，而在胶带剥离前或初始损伤形成后使用双功能 TLR7/9 抑制剂治疗可显着减少皮肤损伤。这些数据表明TLR7和TLR9信号传导抑制剂对于界面皮炎的治疗具有潜在的治疗应用。
Lupus-prone mice develop a chronic inflammatory response to cutaneous injury that depends on the production of type I interferon, TLR7, and TLR9. Recognition of endogenous DNA and RNA by cells expressing TLR7 and TLR9 is an important contributor to the pathogenesis of systemic lupus erythematosus and has been suggested to contribute to cutaneous lupus and to a group of related inflammatory skin diseases termed interface dermatitis. We have developed a mouse model of TLR7- and TLR9-dependent skin inflammation using tape stripping. In normal mice, this resulted in a rapid but transient inflammatory cell infiltration accompanied by induction of type I IFN production by plasmacytoid dendritic cells (PDCs) and release of extracellular traps and proinflammatory cytokines by neutrophils. These responses were strongly reduced in MyD88-deficient mice and in mice treated with a bifunctional inhibitor of TLR7 and TLR9. In contrast, in lupus-prone (NZBxNZW)F1 mice, tape stripping induced the development of chronic lesions characterized by a persistent type I IFN gene signature and many clinical and histological features of cutaneous lupus. Depletion of PDCs before injury prevented the development of skin lesions, whereas treatment with a bifunctional TLR7/9 inhibitor before tape stripping or after the initial lesion was established led to a significant reduction of the disease. These data suggest that inhibitors of TLR7 and TLR9 signaling have potential therapeutic application for the treatment of interface dermatitis.
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影响因子：
13.5
作者：
Bamboat, Zubin M.;Balachandran, Vinod P.;Ocuin, Lee M.;Obaid, Hebroon;Plitas, George;DeMatteo, Ronald P.
通讯作者：
DeMatteo, Ronald P.
干扰素诱导的IFI200家族基因在全身性红斑狼疮中。
影响因子：
4.4
作者：
Choubey, Divaker;Panchanathan, Ravichandran
通讯作者：
Panchanathan, Ravichandran
影响因子：
--
作者：
Clancy, RM;Backer, CB;Buyon, JP
通讯作者：
Buyon, JP
影响因子：
10.8
作者：
Inoue, J;Yotsumoto, S;Aramaki, Y
通讯作者：
Aramaki, Y
影响因子：
82.9
作者：
通讯作者：
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