Differential influences of the aryl hydrocarbon receptor on Th17 mediated responses in vitro and in vivo.
Differential influences of the aryl hydrocarbon receptor on Th17 mediated responses in vitro and in vivo.
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DOI：
10.1371/journal.pone.0079819
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Stockinger B
中科院分区：
文献类型：
--
作者：
Duarte JH;Di Meglio P;Hirota K;Ahlfors H;Stockinger B
芳烃受体(AhR)通过诱导调节性T细胞在实验性自身免疫性脑脊髓炎(EAE)的病理免疫反应中具有抗炎作用。与以前发表的结果一致，我们发现TCDD对EAE具有保护作用，然而，这种免疫调节作用不是新生Treg产生的结果，而是抑制Th17细胞分化的结果。免疫时全身应用FICZ也减少了EAE的病理，尽管程度比TCDD轻。在包括TCDD在内的AhR激动剂存在下，Th17的体外分化促进了IL-17和IL-22的表达，但不能诱导Treg的分化。AHR亲和力影响Th17细胞分泌IL-17和IL-22蛋白的量，但似乎不影响体内对EAE的易感性。利用条件性AhR缺陷小鼠，我们发现TCDD的抗炎作用依赖于T细胞和树突状细胞中AhR的激活，进一步强调了TCDD在体内干扰T效应细胞分化的能力。AhR的体内和体外效应之间的二分法揭示了AhR途径的复杂性，该途径具有影响参与建立免疫反应的不同AhR表达的细胞类型的能力，从而参与决定其结果。
The aryl hydrocarbon receptor (AhR) has been attributed with anti-inflammatory effects in the development of pathological immune responses leading to experimental autoimmune encephalomyelitis (EAE) via the induction of regulatory T cells. In agreement with previously published findings, we find that TCDD administration confers protection from EAE, however, this immuno-modulatory effect was not the consequence of de novo Treg generation, but the inhibition of Th17 cell differentiation. Systemic application of FICZ at the time of immunization also reduced EAE pathology albeit to a lesser degree than TCDD. In vitro Th17 differentiation in the presence of AhR agonists, including TCDD, promoted IL-17 and IL-22 expression, but did not induce Treg differentiation. AhR affinity influenced the amounts of IL-17 and IL-22 protein that was secreted by Th17 cells, but did not seem to affect susceptibility to EAE in vivo. Making use of conditional AhR-deficient mice, we show that the anti-inflammatory effect of TCDD depends on AhR activation in both T cells and dendritic cells, further emphasising the ability of TCDD to interfere with T effector cell differentiation in vivo. The dichotomy between the in vivo and in vitro effects of AhR reveals the complexity of the AhR pathway, which has the capacity of affecting different AhR-expressing cell types involved in mounting immune responses, thus participating in defining their outcome.
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影响因子：
64.5
作者：
Ivanov, Ivaylo I.;McKenzie, Brent S.;Littman, Dan R.
通讯作者：
Littman, Dan R.
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
3.7
作者：
Romme Christensen J;Börnsen L;Ratzer R;Piehl F;Khademi M;Olsson T;Sørensen PS;Sellebjerg F
通讯作者：
Sellebjerg F
DOI：
10.1084/jem.20062648
发表时间：
2007-07-09
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Caton ML;Smith-Raska MR;Reizis B
通讯作者：
Reizis B
影响因子：
8.8
作者：
Miniero, R;De Felip, E;di Domenico, A
通讯作者：
di Domenico, A