Activation of the aryl hydrocarbon receptor dampens the severity of inflammatory skin conditions.
Activation of the aryl hydrocarbon receptor dampens the severity of inflammatory skin conditions.
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DOI：
10.1016/j.immuni.2014.04.019
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发表时间：
2014-06-19
期刊：
影响因子：
32.4
通讯作者：
Stockinger, Brigitta
中科院分区：
文献类型：
--
作者：
Di Meglio, Paola;Duarte, Joao H.;Ahlfors, Helena;Owens, Nick D. L.;Li, Ying;Villanova, Federica;Tosi, Isabella;Hirota, Keiji;Nestle, Frank O.;Mrowietz, Ulrich;Gilchrist, Michael J.;Stockinger, Brigitta
已知环境刺激有助于银屑病和其他自身免疫性疾病的发病机制，但其机制在很大程度上是未知的。在这里，我们表明，芳香烃受体（AhR），一个转录因子，感觉环境刺激，调制银屑病的病理。AhR激活配体减少银屑病患者皮损中的炎症，而AhR拮抗剂增加炎症。类似地，通过内源性配体FICZ的AhR信号传导减少了咪喹莫特诱导的皮肤炎症模型中的炎症反应，并且与AhR充足的对照相比，AhR缺陷小鼠表现出疾病的实质性恶化。非造血细胞，特别是角质形成细胞，负责这种过度炎症反应，其中涉及转录因子的AP-1家族成员的上调。因此，我们的数据表明AhR在炎症反应的调节中起着关键作用，并为慢性炎症性疾病的新治疗策略提供了可能性。生理AhR信号减少患者活检中的银屑病基因表达阻断AhR信号加剧患者活检中的银屑病基因表达AhR缺陷小鼠在咪喹莫特模型中显示加剧的皮肤炎症小鼠或人角质形成细胞上AhR的缺失导致过度炎症芳烃受体（AhR），一种响应环境信号的转录因子，与参与炎症反应的广泛基因相互作用。Di Meglio等人显示AhR生理刺激改善小鼠和人的皮肤炎症。
Environmental stimuli are known to contribute to psoriasis pathogenesis and that of other autoimmune diseases, but the mechanisms are largely unknown. Here we show that the aryl hydrocarbon receptor (AhR), a transcription factor that senses environmental stimuli, modulates pathology in psoriasis. AhR-activating ligands reduced inflammation in the lesional skin of psoriasis patients, whereas AhR antagonists increased inflammation. Similarly, AhR signaling via the endogenous ligand FICZ reduced the inflammatory response in the imiquimod-induced model of skin inflammation and AhR-deficient mice exhibited a substantial exacerbation of the disease, compared to AhR-sufficient controls. Nonhematopoietic cells, in particular keratinocytes, were responsible for this hyperinflammatory response, which involved upregulation of AP-1 family members of transcription factors. Thus, our data suggest a critical role for AhR in the regulation of inflammatory responses and open the possibility for novel therapeutic strategies in chronic inflammatory disorders. Physiological AhR signals reduce psoriasis gene expression in patient biopsies Blocking AhR signals exacerbates psoriasis gene expression in patient biopsies AhR-deficient mice show exacerbated skin inflammation in imiquimod model Absence of AhR on mouse or human keratinocytes causes excessive inflammation The aryl hydrocarbon receptor (AhR), a transcription factor that responds to environmental signals, interacts with a wide range of genes involved in inflammatory responses. Di Meglio et al. show that physiological stimulation of AhR ameliorates skin inflammation in mice and humans.
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影响因子：
30.5
作者：
通讯作者：
--
影响因子：
3.7
作者：
Duarte JH;Di Meglio P;Hirota K;Ahlfors H;Stockinger B
通讯作者：
Stockinger B
影响因子：
3.5
作者：
Bowcock, AM;Shannon, W;Menter, A
通讯作者：
Menter, A
DOI：
10.1073/pnas.0701764104
发表时间：
2007-05-22
影响因子：
11.1
作者：
Fritsche, Ellen;Schaefer, Claudia;Krutmann, Jean
通讯作者：
Krutmann, Jean
影响因子：
6.5
作者：
Girardi, Michael;Lewis, Julia M.;Tigelaar, Robert E.
通讯作者：
Tigelaar, Robert E.