The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins
The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins
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DOI：
10.1038/nature06881
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发表时间：
2008-05-01
期刊：
影响因子：
64.8
通讯作者：
Stockinger, Brigitta
中科院分区：
文献类型：
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作者：
Veldhoen, Marc;Hirota, Keiji;Stockinger, Brigitta
芳烃受体（AHR）是一种配体依赖性转录因子，最为人所知的是介导二恶英的毒性（1）。环境因素被认为是导致自身免疫性疾病发病率增加的原因，其中许多是由于T（H）17 T细胞的活性，T（H）17 T细胞是一种新的辅助性T细胞亚群，其特征在于产生细胞因子IL- 17。在这里，我们表明，在小鼠的CD 4（+）T-细胞谱系中，AHR表达仅限于T（H）17细胞亚群，其连接导致T（H）17细胞因子白细胞介素（IL）-22的产生。AHR也在人T（H）17细胞中表达。在T（H）17细胞发育期间，高亲和力配体激活AHR显著增加T（H）17 T细胞的比例及其细胞因子的产生。来自AHR缺陷型小鼠的CD 4（+）T细胞可以产生T（H）17细胞应答，但是当与AHR配体对抗时不能产生IL- 22，并且不显示增强的T（H）17细胞发育。在实验性自身免疫性脑脊髓炎诱导过程中AHR激活导致野生型小鼠的加速发作和病理学增加，但不导致AHR缺陷型小鼠。因此，AHR配体可能代表自身免疫性疾病发展中的辅因子。
The aryl hydrocarbon receptor ( AHR) is a ligand- dependent transcription factor best known for mediating the toxicity of dioxin(1). Environmental factors are believed to contribute to the increased prevalence of autoimmune diseases, many of which are due to the activity of T(H)17 T cells, a new helper T- cell subset characterized by the production of the cytokine IL- 17. Here we show that in the CD4(+) T- cell lineage of mice AHR expression is restricted to the T(H)17 cell subset and its ligation results in the production of the T(H)17 cytokine interleukin ( IL)- 22. AHR is also expressed in human T(H)17 cells. Activation of AHR by a high-affinity ligand during T(H)17 cell development markedly increases the proportion of T(H)17 T cells and their production of cytokines. CD4(+) T cells from AHR- deficient mice can develop T(H)17 cell responses, but when confronted with AHR ligand fail to produce IL- 22 and do not show enhanced T(H)17 cell development. AHR activation during induction of experimental autoimmune encephalomyelitis causes accelerated onset and increased pathology in wild- type mice, but not AHR- deficient mice. AHR ligands may therefore represent co- factors in the development of autoimmune diseases.