Ambient particulate matter activates the aryl hydrocarbon receptor in dendritic cells and enhances Th17 polarization.
Ambient particulate matter activates the aryl hydrocarbon receptor in dendritic cells and enhances Th17 polarization.
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DOI：
10.1016/j.toxlet.2018.04.020
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发表时间：
2018-08
影响因子：
3.5
通讯作者：
Vogel CFA
中科院分区：
文献类型：
--
作者：
Castañeda AR;Pinkerton KE;Bein KJ;Magaña-Méndez A;Yang HT;Ashwood P;Vogel CFA
本研究的目的是探讨芳烃受体（AhR）在环境颗粒物（PM）介导的树突状细胞（DC）的激活和Th 17免疫反应的体外作用。为了评估AhR在PM介导的DC活化、共刺激和细胞因子表达中的潜在作用，用PM处理来自C57 BL 6野生型或AhR敲除（AhR-/-）小鼠的骨髓（BM）衍生的巨噬细胞和DC。通过野生型或AhR−/− BMDC与自体初始T细胞的共培养来评估Th 17分化。PM2.5显著诱导AhR DNA与二恶英反应元件（DRE）的结合活性以及AhR阻遏物（AhRR）、细胞色素P450（CYP）1A 1和CYP 1B 1的表达，表明AhR被激活。在活化的（OVA致敏的）BMDC中，PM2.5诱导白细胞介素（IL）-1β、CD 80、CD 86和MHC II类，表明增强的DC活化、共刺激和抗原呈递;在AhR缺陷型DC中消除的应答。用PM和脂多糖（LPS）处理的DC-T细胞共培养物导致IL-17 A和IL-22在mRNA水平上的表达升高，这是由AhR介导的。PM处理的DC在赋予T细胞Th 17表型中是必不可少的，这与MHC II类和环氧合酶（考克斯）-2的表达增强有关。总之，PM增强DC活化，其以AhR依赖性方式引发幼稚T细胞向Th 17样表型分化。
The objective of this study was to explore the role of the aryl hydrocarbon receptor (AhR) in ambient particulate matter (PM)-mediated activation of dendritic cells (DCs) and Th17-immune responses in vitro. To assess the potential role of the AhR in PM-mediated activation of DCs, co-stimulation, and cytokine expression, bone marrow (BM)-derived macrophages and DCs from C57BL6 wildtype or AhR knockout (AhR−/−) mice were treated with PM. Th17 differentiation was assessed via co-cultures of wildtype or AhR−/− BMDCs with autologous naive T cells. PM2.5 significantly induced AhR DNA binding activity to dioxin responsive elements (DRE) and expression of the AhR repressor (AhRR), cytochrome P450 (CYP) 1A1, and CYP1B1, indicating activation of the AhR. In activated (OVA sensitized) BMDCs, PM2.5 induced interleukin (IL)-1β, CD80, CD86, and MHC class II, suggesting enhanced DC activation, co-stimulation, and antigen presentation; responses that were abolished in AhR deficient DCs. DC-T cell co-cultures treated with PM and lipopolysaccharide (LPS) led to elevated IL-17A and IL-22 expression at the mRNA level, which is mediated by the AhR. PM-treated DCs were essential in endowing T cells with a Th17-phenotype, which was associated with enhanced expression of MHC class II and cyclooxygenase (COX)-2. In conclusion, PM enhances DC activation that primes naive T cell differentiation towards a Th17-like phenotype in an AhR-dependent manner.
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DOI：
10.1080/15287394.2016.1222920
发表时间：
2017
期刊：
Journal of toxicology and environmental health. Part A
影响因子：
--
作者：
Castañeda AR;Bein KJ;Smiley-Jewell S;Pinkerton KE
通讯作者：
Pinkerton KE
影响因子：
5
作者：
Bein, K. J.;Wexler, A. S.
通讯作者：
Wexler, A. S.
影响因子：
120.7
作者：
Dominici, F;Peng, RD;Samet, JM
通讯作者：
Samet, JM
影响因子：
4.6
作者：
DiNatale, Brett C.;Schroeder, Jennifer C.;Perdew, Gary H.
通讯作者：
Perdew, Gary H.
影响因子：
6.1
作者：
Kado S;Chang WLW;Chi AN;Wolny M;Shepherd DM;Vogel CFA
通讯作者：
Vogel CFA