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芳烃受体(AhR)在自身免疫调节中的作用及其作为针对CD4 T细胞介导的炎症性疾病治疗靶点的潜力。

The role of AhR in autoimmune regulation and its potential as a therapeutic target against CD4 T cell mediated inflammatory disorder.

作者信息

Zhu Conghui, Xie Qunhui, Zhao Bin

机构信息

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.

出版信息

Int J Mol Sci. 2014 Jun 5;15(6):10116-35. doi: 10.3390/ijms150610116.

Abstract

AhR has recently emerged as a critical physiological regulator of immune responses affecting both innate and adaptive systems. Since the AhR signaling pathway represents an important link between environmental stimulators and immune-mediated inflammatory disorder, it has become the object of great interest among researchers recently. The current review discusses new insights into the mechanisms of action of a select group of inflammatory autoimmune diseases and the ligand-activated AhR signaling pathway. Representative ligands of AhR, both exogenous and endogenous, are also reviewed relative to their potential use as tools for understanding the role of AhR and as potential therapeutics for the treatment of various inflammatory autoimmune diseases, with a focus on CD4 helper T cells, which play important roles both in self-immune tolerance and in inflammatory autoimmune diseases. Evidence indicating the potential use of these ligands in regulating inflammation in various diseases is highlighted, and potential mechanisms of action causing immune system effects mediated by AhR signaling are also discussed. The current review will contribute to a better understanding of the role of AhR and its signaling pathway in CD4 helper T cell mediated inflammatory disorder. Considering the established importance of AhR in immune regulation and its potential as a therapeutic target, we also think that both further investigation into the molecular mechanisms of immune regulation that are mediated by the ligand-specific AhR signaling pathway, and integrated research and development of new therapeutic drug candidates targeting the AhR signaling pathway should be pursued urgently.

摘要

芳烃受体(AhR)最近已成为影响先天性和适应性免疫系统的免疫反应的关键生理调节因子。由于AhR信号通路是环境刺激物与免疫介导的炎症性疾病之间的重要联系,它最近已成为研究人员极大兴趣的对象。本综述讨论了对一组特定炎症性自身免疫疾病的作用机制以及配体激活的AhR信号通路的新见解。还综述了AhR的代表性配体,包括外源性和内源性配体,相对于它们作为理解AhR作用的工具以及作为治疗各种炎症性自身免疫疾病的潜在疗法的潜在用途,重点是在自身免疫耐受和炎症性自身免疫疾病中均起重要作用的CD4辅助性T细胞。强调了表明这些配体在调节各种疾病炎症方面潜在用途的证据,并讨论了由AhR信号介导的引起免疫系统效应的潜在作用机制。本综述将有助于更好地理解AhR及其信号通路在CD4辅助性T细胞介导的炎症性疾病中的作用。考虑到AhR在免疫调节中的既定重要性及其作为治疗靶点的潜力,我们还认为应迫切开展对由配体特异性AhR信号通路介导的免疫调节分子机制的进一步研究,以及针对AhR信号通路的新治疗候选药物的综合研发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d065/4100143/58bd07199d0b/ijms-15-10116-g001.jpg

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