Regulation of Skin Barrier Function via Competition between AHR Axis versus IL-13/IL-4‒JAK‒STAT6/STAT3 Axis: Pathogenic and Therapeutic Implications in Atopic Dermatitis.

Regulation of Skin Barrier Function via Competition between AHR Axis versus IL-13/IL-4‒JAK‒STAT6/STAT3 Axis: Pathogenic and Therapeutic Implications in Atopic Dermatitis.
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通过芳香烃受体(AHR)轴与白细胞介素 - 13/白细胞介素 - 4 - Janus激酶 - 信号转导及转录激活因子6/信号转导及转录激活因子3(IL - 13/IL - 4‒JAK‒STAT6/STAT3)轴之间的竞争对皮肤屏障功能的调节:特应性皮炎中的致病和治疗意义

DOI:
10.3390/jcm9113741
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发表时间:
2020-11-20
影响因子:
3.9
通讯作者:
Furue M
Furue M
中科院分区:
医学2区
文献类型:
--
作者:
Furue M

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特应性皮炎(AD)的特征是皮肤炎症、屏障功能障碍和慢性瘙痒。由于抗白细胞介素 4 (IL-4) 受体 α 抗体 dupilumab 改善了 AD 的所有三个主要特征,因此 2 型细胞因子 IL-4,尤其是 IL-13 已被表明在 AD 中具有致病意义。越来越多的证据表明,皮肤屏障功能是通过芳烃受体 (AHR) 轴(屏障上调)和 IL-13/IL-4-JAK-STAT6/STAT3 轴(屏障下调)之间的竞争来调节的。后一个轴还会诱发氧化应激,从而加剧炎症。传统和最近开发的治疗 AD 的药物,如类固醇、钙调神经磷酸酶抑制剂、环孢素、dupilumab 和 JAK 抑制剂,会抑制 IL-13/IL-4-JAK-STAT6/STAT3 轴,而煤焦油和 glyteer 等较旧的药物是抗氧化 AHR 激动剂。在本文中,我总结了 IL-13/IL-4-JAK-STAT6/STAT3 轴和 AHR 轴在 AD 中的致病和治疗意义。
Atopic dermatitis (AD) is characterized by skin inflammation, barrier dysfunction, and chronic pruritus. As the anti-interleukin-4 (IL-4) receptor α antibody dupilumab improves all three cardinal features of AD, the type 2 cytokines IL-4 and especially IL-13 have been indicated to have pathogenic significance in AD. Accumulating evidence has shown that the skin barrier function is regulated via competition between the aryl hydrocarbon receptor (AHR) axis (up-regulation of barrier) and the IL-13/IL-4‒JAK‒STAT6/STAT3 axis (down-regulation of barrier). This latter axis also induces oxidative stress, which exacerbates inflammation. Conventional and recently developed agents for treating AD such as steroid, calcineurin inhibitors, cyclosporine, dupilumab, and JAK inhibitors inhibit the IL-13/IL-4‒JAK‒STAT6/STAT3 axis, while older remedies such as coal tar and glyteer are antioxidative AHR agonists. In this article, I summarize the pathogenic and therapeutic implications of the IL-13/IL-4‒JAK‒STAT6/STAT3 axis and the AHR axis in AD.
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