Aryl Hydrocarbon Receptor Signaling Synergizes with TLR/NF-κB-Signaling for Induction of IL-22 Through Canonical and Non-Canonical AhR Pathways.
Aryl Hydrocarbon Receptor Signaling Synergizes with TLR/NF-κB-Signaling for Induction of IL-22 Through Canonical and Non-Canonical AhR Pathways.
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DOI：
10.3389/ftox.2021.787360
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发表时间：
2021
影响因子：
--
通讯作者：
Vogel CFA
中科院分区：
文献类型：
--
作者：
Ishihara Y;Kado SY;Bein KJ;He Y;Pouraryan AA;Urban A;Haarmann-Stemmann T;Sweeney C;Vogel CFA
白介素22(IL-22)在肠道免疫和宿主防御中起重要作用，主要由活化的T细胞产生。在不同的情况下，IL-22可能参与病理状态或作为一种促进肿瘤的细胞因子由浸润性免疫细胞分泌。在这里，我们发现，当细胞通过Toll样受体(TLR)家族激活时，骨髓来源的巨噬细胞(BMM)在芳香烃受体(AhR)激活后表达并产生IL-22。AhR的额外激活在TLR激活的BMM中触发了IL-22的显著诱导。IL-22启动子的缺失和突变构建揭示了共同的DRE和RelBAhRE结合元件对于介导AhR和TLR配体的协同作用是必要的。抑制研究和对来自基因敲除小鼠的骨髓基质细胞的分析证实，AhR和TLR配体对IL-22的协同诱导依赖于AhR和核因子-kappaB(NF-κB)成员RelB的表达。从交通相关的空气污染(TRAP)和野火中收集的颗粒物(PM)的暴露激活了AhR和NF-κB信号，并显著诱导了IL-22的表达。综上所述，本研究表明，AhR和NF-κB信号通路的同时激活通过整合规范和非典型AhR途径的信号而导致IL-22的协同和延长诱导。
Interleukin 22 (IL-22) is critically involved in gut immunity and host defense and primarily produced by activated T cells. In different circumstances IL-22 may contribute to pathological conditions or act as a cancer promoting cytokine secreted by infiltrating immune cells. Here we show that bone marrow-derived macrophages (BMM) express and produce IL-22 after activation of the aryl hydrocarbon receptor (AhR) when cells are activated through the Toll-like receptor (TLR) family. The additional activation of AhR triggered a significant induction of IL-22 in TLR-activated BMM. Deletion and mutation constructs of the IL-22 promoter revealed that a consensus DRE and RelBAhRE binding element are necessary to mediate the synergistic effects of AhR and TLR ligands. Inhibitor studies and analysis of BMM derived from knockout mice confirmed that the synergistic induction of IL-22 by AhR and TLR ligands depend on the expression of AhR and Nuclear Factor-kappa B (NF-κB) member RelB. The exposure to particulate matter (PM) collected from traffic related air pollution (TRAP) and wildfires activated AhR as well as NF-κB signaling and significantly induced the expression of IL-22. In summary this study shows that simultaneous activation of the AhR and NF-κB signaling pathways leads to synergistic and prolonged induction of IL-22 by integrating signals of the canonical and non-canonical AhR pathway.
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影响因子：
10.4
作者：
Edwards S;Zhao G;Tran J;Patten KT;Valenzuela A;Wallis C;Bein KJ;Wexler AS;Lein PJ;Rao X
通讯作者：
Rao X
影响因子：
32.4
作者：
Dmitrieva-Posocco, Oxana;Dzutsev, Amiran;Grivennikov, Sergei, I
通讯作者：
Grivennikov, Sergei, I
影响因子：
5
作者：
Bein, K. J.;Wexler, A. S.
通讯作者：
Wexler, A. S.
影响因子：
5
作者：
D'Evelyn, S. M.;Vogel, C. F. A.;Pinkerton, K. E.
通讯作者：
Pinkerton, K. E.
影响因子：
14.9
作者：
Heinemeyer, T;Wingender, E;Kolchanov, NA
通讯作者：
Kolchanov, NA