Aryl Hydrocarbon Receptor in Cutaneous Vascular Endothelial Cells Restricts Psoriasis Development by Negatively Regulating Neutrophil Recruitment.
Aryl Hydrocarbon Receptor in Cutaneous Vascular Endothelial Cells Restricts Psoriasis Development by Negatively Regulating Neutrophil Recruitment.
复制标题
皮肤血管内皮细胞中的芳基烃受体通过负调节中性粒细胞的募集来限制银屑病的发展。
DOI：
10.1016/j.jid.2019.11.022
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发表时间：
2019-12
影响因子：
6.5
通讯作者：
Gang Wang
中科院分区：
文献类型：
--
作者：
Zhenlai Zhu;Jiaoling Chen;Yiting Lin;Chen Zhang;Wei Li;Hongjiang Qiao;Meng Fu;Erle Dang;Gang Wang
血管内皮细胞(VECs)排列在血管内部，参与生理和炎症过程。所有皮肤细胞类型都表达芳香烃受体(AhR)，这与银屑病的发病机制有关。然而，皮肤VEC AhR在银屑病发病机制中的作用仍不清楚。在本研究中，我们发现在银屑病患者血管内皮细胞中AhR蛋白的表达和激活均下调。建立了皮肤血管内皮细胞特异性AhR基因敲除小鼠(AhR cVECs-KO)。使用咪喹莫特(Imquimod，ImQ)和IL-23诱导的银屑病模型，我们发现在AhR cVECs-KO小鼠中，过度的中性粒细胞募集加剧了皮肤炎症。中性粒细胞中和减轻ImQ处理的AhR cVECs-KO小鼠加重的炎症。此外，AhR cVECs-KO小鼠的皮肤血管内皮细胞与对照组相比表现出更多的扩张和激活。此外，在促炎细胞因子刺激下，AhR缺陷的微血管内皮细胞在体内和体外均显示ICAM-1表达增加，这可能促进了中性粒细胞的募集。综上所述，我们的研究表明，真皮血管内皮细胞中的AhR通过负向调节中性粒细胞募集来限制银屑病的发展，从而为银屑病的发病机制提供了以前未见报道的见解。
Vascular endothelial cells (VECs) that line the interiors of blood vessels participate in physiological and inflammatory processes. All skin cell types express.the aryl hydrocarbon receptor (AhR), which is involved in the pathogenesis of psoriasis. However, the role of the cutaneous VEC AhR in the pathogenesis of psoriasis remains elusive. In the present study, we found that AhR protein expression and activation were downregulated in psoriatic VECs. Furthermore, cutaneous VEC-specific AhR-knockout (AhR cVECs-KO ) mice were established. Using imiquimod (IMQ) and IL-23-induced psoriasis models, we found that skin inflammation was exacerbated with excessive neutrophil recruitment in AhR cVECs-KO mice. And neutrophil neutralization alleviates exacerbated inflammation in IMQ-treated AhR cVECs-KO mice. In addition, cutaneous VECs in AhR cVECs-KO mice exhibited increased dilation and activation compared with those in control mice. Furthermore, AhR-deficient microvascular endothelial cells stimulated by proinflammatory cytokines showed increased ICAM-1 expression in vivo and in vitro, which may have facilitated neutrophil recruitment. In summary, our study demonstrates that AhR in dermal VECs restricts psoriasis development by negatively regulating neutrophil recruitment, thereby providing previously unreported insight into the pathogenesis of psoriasis.
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影响因子：
4.6
作者：
Hu SC;Yu HS;Yen FL;Lin CL;Chen GS;Lan CC
通讯作者：
Lan CC
影响因子：
82.9
作者：
Rothhammer V;Mascanfroni ID;Bunse L;Takenaka MC;Kenison JE;Mayo L;Chao CC;Patel B;Yan R;Blain M;Alvarez JI;Kébir H;Anandasabapathy N;Izquierdo G;Jung S;Obholzer N;Pochet N;Clish CB;Prinz M;Prat A;Antel J;Quintana FJ
通讯作者：
Quintana FJ
影响因子：
6.5
作者：
Haas, Katharina;Weighardt, Heike;Esser, Charlotte
通讯作者：
Esser, Charlotte
影响因子：
29.4
作者：
Monteleone, Ivan;Rizzo, Angelamaria;Monteleone, Giovanni
通讯作者：
Monteleone, Giovanni
影响因子：
64.5
作者：
Crewe C;Joffin N;Rutkowski JM;Kim M;Zhang F;Towler DA;Gordillo R;Scherer PE
通讯作者：
Scherer PE