The aryl hydrocarbon receptor at the forefront of host-microbe interactions in the skin: A perspective on current knowledge gaps and directions for future research and therapeutic applications.
The aryl hydrocarbon receptor at the forefront of host-microbe interactions in the skin: A perspective on current knowledge gaps and directions for future research and therapeutic applications.
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DOI：
10.1111/exd.14409
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发表时间：
2021-10
影响因子：
3.6
通讯作者：
Perdew GH
中科院分区：
文献类型：
--
作者：
van den Bogaard EH;Esser C;Perdew GH
皮肤是包括细菌、病毒和真菌在内的皮肤微生物群落的家园，这些微生物被广泛认为对皮肤动态平衡很重要，但也与皮肤病有关。关于皮肤微生物区系组成及其在一些皮肤病中的变化的详细知识可用。然而，微生物与宿主皮肤细胞之间的具体相互作用或它们如何相互沟通还不太清楚。为了识别、理解并最终在治疗上利用微生物失调与疾病的因果关系，需要研究涉及宿主-微生物相互作用的受体和介体。在这篇透视文章中，我们提供了一个这样的受体，即芳烃受体(AHR)的展望。众所周知，AHR是一种配体激活的转录因子，调节皮肤中存在的许多细胞类型的增殖、分化和功能。以煤焦油和Tapinarof等抗炎药物为靶点，对特应性皮炎和牛皮癣有效。AHR信号在多种小化学物质或配体结合时被激活，包括微生物区系衍生的代谢物。新的证据表明，通过皮肤微生物区系衍生的代谢物，表皮AHR信号的关键作用。因此，AHR驱动的抗菌肽的表达和角质层的形成可能会改变皮肤微生物区系的组成。这是一个自我延续的反馈循环，需要新的治疗干预策略，我们在此讨论未来机制研究的要求。
The skin is home to a community of skin microbiota including bacteria, viruses and fungi, which are widely accepted to be of importance for skin homeostasis but also associated with skin diseases. Detailed knowledge on the skin microbiota composition and its changes in a number of skin diseases is available. Yet, specific interactions between microbes and the host skin cells or how they communicate with each other are less well understood. To identify, understand and eventually therapeutically exploit causal relationships of microbial dysbiosis with disease, studies are required that address the receptors and mediators involved in host‐microbe interactions. In this perspective article, we provide an outlook on one of such receptors, namely the aryl hydrocarbon receptor (AHR). The AHR is well known for being a ligand‐activated transcription factor regulating the proliferation, differentiation and function of many cell types present in the skin. Its targeting by anti‐inflammatory therapeutics such as coal tar and Tapinarof is effective in atopic dermatitis and psoriasis. AHR signalling is activated upon binding of wide variety of small chemicals or ligands, including microbiota‐derived metabolites. New evidence has emerged pointing towards a key role for epidermal AHR signalling through skin microbiota‐derived metabolites. In response, AHR‐driven expression of antimicrobial peptides and stratum corneum formation may alter the skin microbiota composition. This a self‐perpetuating feedback loop calls for novel therapeutic intervention strategies for which we herein discuss the requirements in future mechanistic studies.
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