A Critical Role of the IL-1β-IL-1R Signaling Pathway in Skin Inflammation and Psoriasis Pathogenesis.
A Critical Role of the IL-1β-IL-1R Signaling Pathway in Skin Inflammation and Psoriasis Pathogenesis.
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IL-1β-IL-1R信号通路在皮肤炎症和牛皮癣发病机理中的关键作用。
DOI：
10.1016/j.jid.2018.07.025
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发表时间：
2019-01
期刊：
影响因子：
--
通讯作者：
Yan J
中科院分区：
文献类型：
--
作者：
Cai Y;Xue F;Quan C;Qu M;Liu N;Zhang Y;Fleming C;Hu X;Zhang HG;Weichselbaum R;Fu YX;Tieri D;Rouchka EC;Zheng J;Yan J
IL-1信号通路在银屑病等慢性自身炎症性皮肤病的发病机制中起着重要作用。然而，确切的细胞和分子机制尚未完全了解。在这里，我们发现IL-1β在银屑病皮损皮肤和咪喹莫特（IMQ）治疗的小鼠皮肤中显著升高。此外，IL-1 R信号似乎与银屑病疾病进展和治疗反应相关。真皮γδ T细胞和其他细胞如角质形成细胞中的IL-1信号传导对于MQ诱导的皮肤炎症是必不可少的。IL-1β诱导小鼠真皮γδ T细胞增殖和IL-17产生。此外，IL-1β刺激角质形成细胞分泌趋化因子，这些趋化因子优先化学吸引能够产生γδ T细胞（γδT17）的外周CD 27 − CCR 6 +IL-17。进一步的研究表明，内源性IL-1β分泌受皮肤细胞调节，以维持小鼠真皮γδT17稳态。与棒状杆菌相关的小鼠皮肤，人类银屑病皮损中富集的细菌增加了IL-1β和真皮γδT17细胞扩增。因此，IL-1β-IL-1 R信号通路可能通过直接调节真皮IL-17产生细胞和刺激角质形成细胞放大炎症级联反应而参与皮肤炎症和银屑病发病机制。
IL-1 signaling pathway has been shown to play a critical role in the pathogenesis of chronic, autoinflammatory skin diseases such as psoriasis. However, the exact cellular and molecular mechanisms have not been fully understood. Here, we show that IL-1β is significantly elevated in psoriatic lesional skin and imiquimod (IMQ)-treated mouse skin. In addition, IL-1R signaling appears to correlate with psoriasis disease progression and treatment response. IL-1 signaling in both dermal γδ T cells and other cells such as keratinocytes is essential to an IMQ-induced skin inflammation. IL-1β induces dermal γδ T cell proliferation and IL-17 production in mice. In addition, IL-1β stimulates keratinocytes to secrete chemokines which preferentially chemoattract peripheral CD27− CCR6+IL-17 capable producing γδ T cells (γδT17). Further studies reveal that endogenous IL-1β secretion is regulated by skin commensals to maintain dermal γδT17 homeostasis in mice. Mouse skin associated with corynebacterium, bacterial enriched in human psoriatic lesional skin has increased IL-1β and dermal γδT17 cell expansion. Thus, IL-1β-IL-1R signaling pathway may contribute to skin inflammation and psoriasis pathogenesis via the direct regulation of dermal IL-17-producing cells and stimulation of keratinocytes for amplifying inflammatory cascade.
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影响因子：
6.5
作者：
COOPER, KD;HAMMERBERG, C;FISHER, G
通讯作者：
FISHER, G
影响因子：
17.1
作者：
Dombrowski Y;Peric M;Koglin S;Kammerbauer C;Göss C;Anz D;Simanski M;Gläser R;Harder J;Hornung V;Gallo RL;Ruzicka T;Besch R;Schauber J
通讯作者：
Schauber J
CD27是干扰素 - 粉状和白介素17产生的伽玛德氏菌T细胞亚群之间平衡的胸腺决定因素。
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
32.4
作者：
St Leger AJ;Desai JV;Drummond RA;Kugadas A;Almaghrabi F;Silver P;Raychaudhuri K;Gadjeva M;Iwakura Y;Lionakis MS;Caspi RR
通讯作者：
Caspi RR
影响因子：
13.8
作者：
Rachakonda, Tara D.;Schupp, Clayton W.;Armstrong, April W.
通讯作者：
Armstrong, April W.