Natural agonists for aryl hydrocarbon receptor in culture medium are essential for optimal differentiation of Th17 T cells.
Natural agonists for aryl hydrocarbon receptor in culture medium are essential for optimal differentiation of Th17 T cells.
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培养基中芳基烃受体的天然激动剂对于Th17 T细胞的最佳分化至关重要。
DOI：
10.1084/jem.20081438
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发表时间：
2009-01-16
期刊：
影响因子：
--
通讯作者：
Stockinger B
中科院分区：
文献类型：
--
作者：
Veldhoen M;Hirota K;Christensen J;O'Garra A;Stockinger B
Th 17细胞的分化依赖于白细胞介素（IL）-6和转化生长因子（TGF）-β，并通过芳烃受体（AhR）的活化来调节。在这项研究中，我们表明，分化的Th 17细胞，但不是Th 1或诱导的调节性T（iT reg）细胞，增加了内源性AhR激动剂存在于培养基中。在AhR拮抗剂CH-223191的存在下，野生型小鼠的Th 17发育是次优的，类似于AhR缺陷小鼠的情况，其显示减弱的IL-17产生而没有IL-22产生。培养基中天然AhR激动剂的存在还通过诱导CYP 1A 1（AhR激活的下游靶点）来揭示。然而，最常用的培养基RPMI支持非常低水平的Th 17极化，而Iscove改良的Dulbecco培养基，一种富含芳香族氨基酸的培养基，其产生AhR激动剂，在小鼠和人细胞中始终导致更高的Th 17扩增。RPMI培养基中AhR激动剂的相对缺乏，加上存在有利于IL-2活化和增强的Stat 5磷酸化的因子，共同对抗最佳的Th 17分化。我们的数据强调，AhR激活在Th 17细胞的发育中起着重要作用，并为大多数小鼠和人细胞的出版物中报道的Th 17细胞的体外极化差提供了合理的解释。
Th17 cell differentiation is dependent on interleukin (IL)-6 and transforming growth factor (TGF)-β, and it is modulated by activation of the aryl hydrocarbon receptor (AhR). In this study, we show that differentiation of Th17 cells, but not Th1 or induced regulatory T (iT reg) cells, is increased by endogenous AhR agonists present in culture medium. Th17 development from wild-type mice is suboptimal in the presence of the AhR antagonist CH-223191, similar to the situation in AhR-deficient mice, which show attenuated IL-17 production and no IL-22 production. The presence of natural AhR agonists in culture medium is also revealed by the induction of CYP1A1, a downstream target of AhR activation. However, the most commonly used medium, RPMI, supports very low levels of Th17 polarization, whereas Iscove's modified Dulbecco's medium, a medium richer in aromatic amino acids, which give rise to AhR agonists, consistently results in higher Th17 expansion in both mouse and human cells. The relative paucity of AhR agonists in RPMI medium, coupled with the presence of factors conducive to IL-2 activation and enhanced Stat5 phosphorylation, conspire against optimal Th17 differentiation. Our data emphasize that AhR activation plays an essential part in the development of Th17 cells and provide a rational explanation for the poor in vitro polarization of Th17 cells that is reported in the majority of publications for both mouse and human cells.
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影响因子：
10.4
作者：
Zhang S;Qin C;Safe SH
通讯作者：
Safe SH
影响因子：
32.4
作者：
Veldhoen, M;Hocking, RJ;Stockinger, B
通讯作者：
Stockinger, B
影响因子：
5.1
作者：
PAINE, AJ;FRANCIS, JE
通讯作者：
FRANCIS, JE
DOI：
10.1073/pnas.0804231105
发表时间：
2008-07-15
影响因子：
11.1
作者：
Kimura, Akihiro;Naka, Tetsuji;Kishimoto, Tadamitsu
通讯作者：
Kishimoto, Tadamitsu
影响因子：
15.3
作者：
ISCOVE, NN;MELCHERS, F
通讯作者：
MELCHERS, F