An interaction between kynurenine and the aryl hydrocarbon receptor can generate regulatory T cells.

An interaction between kynurenine and the aryl hydrocarbon receptor can generate regulatory T cells.
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DOI:
10.4049/jimmunol.0903670
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发表时间:
2010-09-15
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Bradfield CA
Bradfield CA
中科院分区:
其他
文献类型:
--
作者:
Mezrich JD;Fechner JH;Zhang X;Johnson BP;Burlingham WJ;Bradfield CA

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芳烃受体(AHR),二恶英的受体,已被称为导致免疫抑制后,结合二恶英。最近发现,该受体可能是T细胞分化为FoxP 3 + T调节细胞相对于TH 17细胞的中心。在本文中,我们证明了犬尿氨酸,在吲哚胺2,3-双加氧酶(IDO)依赖性色氨酸降解途径中的第一个分解产物,激活AHR。我们进一步表明,这种激活导致AHR依赖性T调节细胞的产生。我们还研究了TGF-β对AHR的依赖性,以实现最佳Treg生成,这可能是次要的,因为暴露于TGF-β后,T细胞中观察到该受体的上调。这些结果阐明了IDO与调节性T细胞生成的关系,此外还突出了AHR在T细胞分化中的重要性。所有组织和细胞均来源于小鼠。
The aryl hydrocarbon receptor (AHR), the receptor for dioxin, has been known to cause immunosuppression after binding dioxin. It has recently been discovered that the receptor may be central to T cell differentiation into FoxP3+ T regulatory cells vs. TH17 cells. In this paper we demonstrate that kynurenine, the first breakdown product in the indoleamine 2,3-dioxygenase(IDO)-dependent tryptophan degradation pathway, activates the AHR. We furthermore show that this activation leads to AHR-dependent T regulatory cell generation. We additionally investigate the dependence of TGF-β on the AHR for optimal Treg generation, which may be secondary to the upregulation of this receptor that is seen in T cells after exposure to TGF-β. These results shed light on the relationship of IDO to the generation of regulatory T cells, in addition to highlighting the central importance of the AHR in T cell differentiation. All tissues and cells were derived from mice.
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