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调节芳烃受体(AHR)功能在肠道免疫和炎症方面具有令人兴奋的治疗潜力。

Modulating AHR function offers exciting therapeutic potential in gut immunity and inflammation.

作者信息

Chen Yue, Wang Yadong, Fu Yawei, Yin Yulong, Xu Kang

机构信息

Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, 410125, China.

College of Animal Science and Technology, Henan Agricultural University, Zhengzhou, 450000, China.

出版信息

Cell Biosci. 2023 May 13;13(1):85. doi: 10.1186/s13578-023-01046-y.

Abstract

Aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a classical exogenous synthetic ligand of AHR that has significant immunotoxic effects. Activation of AHR has beneficial effects on intestinal immune responses, but inactivation or overactivation of AHR can lead to intestinal immune dysregulation and even intestinal diseases. Sustained potent activation of AHR by TCDD results in impairment of the intestinal epithelial barrier. However, currently, AHR research has been more focused on elucidating physiologic AHR function than on dioxin toxicity. The appropriate level of AHR activation plays a role in maintaining gut health and protecting against intestinal inflammation. Therefore, AHR offers a crucial target to modulate intestinal immunity and inflammation. Herein, we summarize our current understanding of the relationship between AHR and intestinal immunity, the ways in which AHR affects intestinal immunity and inflammation, the effects of AHR activity on intestinal immunity and inflammation, and the effect of dietary habits on intestinal health through AHR. Finally, we discuss the therapeutic role of AHR in maintaining gut homeostasis and relieving inflammation.

摘要

芳香烃受体(AHR)是一种依赖配体的转录因子。2,3,7,8-四氯二苯并对二恶英(TCDD)是AHR的一种典型外源性合成配体,具有显著的免疫毒性作用。AHR的激活对肠道免疫反应具有有益影响,但AHR的失活或过度激活可导致肠道免疫失调甚至肠道疾病。TCDD持续强力激活AHR会导致肠道上皮屏障受损。然而,目前AHR的研究更多地集中在阐明其生理功能而非二恶英毒性方面。AHR的适度激活水平在维持肠道健康和预防肠道炎症方面发挥作用。因此,AHR为调节肠道免疫和炎症提供了一个关键靶点。在此,我们总结了目前对AHR与肠道免疫之间关系的理解、AHR影响肠道免疫和炎症的方式、AHR活性对肠道免疫和炎症的影响,以及饮食习惯通过AHR对肠道健康的影响。最后,我们讨论了AHR在维持肠道稳态和减轻炎症方面的治疗作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/357f/10182712/960b177c4c76/13578_2023_1046_Fig1_HTML.jpg

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