芳香烃受体调节免疫应答的研究进展
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摘要
芳香烃受体(aryl hydrocarbon receptor,AhR)是一种配体激活的转录因子,可被污染物、微生物、食物和新陈代谢等提供的小分子活化。研究表明,AhR在许多免疫相关的细胞中表达,对健康和疾病的免疫应答起着重要的作用。AhR信号通路构成了环境、新陈代谢与免疫应答之间的分子桥梁。同时由于AhR活性受小分子调控,也构成治疗免疫调节的潜在目标。在这篇综述中,我们主要讨论了AhR信号通路在固有免疫应答和获得免疫应答中的作用。
The aryl hydrocarbon receptor(AhR) is a ligand-activated transcription factor, which can be activated by small molecules from contaminants, microbes, food, and metabolism. Studies have revealed that AhR is expressed in many immune-related cells and plays an important role in healthy and diseased immune system.Therefore, the AhR signaling pathway constitutes a molecular bridge between the environment, metabolism and immune response. Since AhR activity is regulated by small molecules, AhR became to a potential target of the treatment of immune regulation. In this review, we mainly discuss the roles of the AhR signaling pathway in innate and adaptive immune responses.
The aryl hydrocarbon receptor(AhR) is a ligand-activated transcription factor, which can be activated by small molecules from contaminants, microbes, food, and metabolism. Studies have revealed that AhR is expressed in many immune-related cells and plays an important role in healthy and diseased immune system.Therefore, the AhR signaling pathway constitutes a molecular bridge between the environment, metabolism and immune response. Since AhR activity is regulated by small molecules, AhR became to a potential target of the treatment of immune regulation. In this review, we mainly discuss the roles of the AhR signaling pathway in innate and adaptive immune responses.
引文
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[26]Qiu J,Heller JJ,Guo X,et al.The aryl hydrocarbon receptor regulates gut immunity through modulation of innate lymphoid cells[J].Immunity,2012,36(1):92-104.
[27]Winans B,Nagari A,Chae M,et al.Linking the aryl hydrocarbon receptor with altered DNA methylation patterns and developmentally induced aberrant antiviral CD8+T cell responses[J].J Immunol,2015,194(9):4446-4457.
[28]Cibrian D,Saiz ML,de la Fuente H,et al.CD69 controls the uptake of L-tryptophan through LAT1-CD98 and AhR-dependent secretion of IL-22 in psoriasis[J].Nat Immunol,2016,17(8):985-996.
[29]Sherr DH,Monti S.The role of the aryl hydrocarbon receptor in normal and malignant B cell development[J].Semin Immunopathol,2013,35(6):705-716.
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[2]Bersten DC,Sullivan AE,Peet DJ,et al.bHLH-PASproteins in cancer[J].Nat Rev Cancer,2013,13(12):827-841.
[3]朱俊宇,范霞,梁华平.AhR调控炎性细胞因子的研究进展[J].免疫学杂志,2017,33(1):73-77.
[4]Murray IA,Patterson AD,Perdew GH.Aryl hydrocarbon receptor ligands in cancer:friend and foe[J].Nat Rev Cancer,2014,14(12):801-814.
[5]Denison MS,Soshilov AA,He G,et al.Exactly the same but different:promiscuity and diversity in the molecular mechanisms of action of the aryl hydrocarbon(dioxin)receptor[J].Toxicol Sci,2011,124(1):1-22.
[6]Mezrich JD,Fechner JH,Zhang X,et al.An interaction between kynurenine and the aryl hydrocarbon receptor can generate regulatory T cells[J].J Immunol,2010,185(6):3190-3198.
[7]Jin UH,Lee SO,Safe S.Aryl hydrocarbon receptor(AHR)-active pharmaceuticals are selective AHR modulators in MDA-MB-468 and BT474 breast cancer cells[J].JPharmacol Exp Ther,2012,343(2):333-341.
[8]Naumova E,Pawelec G,Mihaylova A.Natural killer cells,ageing and cancer[J].Cancer Immunol Immunother,2016,65(4):367-370.
[9]Shin JH,Zhang L,Murillo Sauca O,et al.Modulation of natural killer cell antitumor activity by the aryl hydrocarbon receptor[J].Proc Natl Acad Sci U S A,2013,110(30):12391-12396.
[10]Wagage S,John B,Krock BL,et al.The aryl hydrocarbon receptor promotes IL-10 production by NK cells[J].JImmunol,2014,192(4):1661-1670.
[11]Zhang LH,Shin JH,Haggadone MD,et al.The aryl hydrocarbon receptor is required for the maintenance of liver-resident natural killer cells[J].J Exp Med,2016,213(11):2249-2257.
[12]Takenaka MC,Quintana FJ.Tolerogenic dendritic cells[J].Semin Immunopathol,2017,39(2):113-120.
[13]Collison LW,Chaturvedi V,Henderson AL,et al.IL-35-mediated induction of a potent regulatory T cell population[J].Nat Immunol,2010,11(12):1093-1101.
[14]Bessede A,Gargaro M,Pallotta MT,et al.Aryl hydrocarbon receptor control of a disease tolerance defence pathway[J].Nature,2014,511(7508):184-190.
[15]Goettel JA,Gandhi R,Kenison JE,et al.AHR activation is protective against colitis driven by T cells in humanized mice[J].Cell Rep,2016,17(5):1318-1329.
[16]Quintana FJ,Murugaiyan G,Farez MF,et al.An endogenous aryl hydrocarbon receptor ligand acts on dendritic cells and T cells to suppress experimental autoimmune encephalomyelitis[J].Proc Natl Acad Sci U SA,2010,107(48):20768-20773.
[17]Quintana FJ,Jin H,Burns EJ,et al.Aiolos promotes TH17differentiation by directly silencing Il2 expression[J].Nat Immunol,2012,13(8):770-777.
[18]Dant TA,Lin KL,Bruce DW,et al.T-cell expression of AhR inhibits the maintenance of pTreg cells in the gastrointestinal tract in acute GVHD[J].Blood,2017,130(3):348-359.
[19]Kaye J,Piryatinsky V,Birnberg T,et al.Laquinimod arrests experimental autoimmune encephalomyelitis by activating the aryl hydrocarbon receptor[J].Proc Natl Acad Sci U S A,2016,113(41):E6145-E6152.
[20]Nugent LF,Shi G,Vistica BP,et al.ITE,a novel endogenous nontoxic aryl hydrocarbon receptor ligand,efficiently suppresses EAU and T-cell-mediated immunity[J].Invest Ophthalmol Vis Sci,2013,54(12):7463-7469.
[21]谭悦,钱龙,李向培,等.芳香烃受体在类风湿关节炎患者外周血CCR6+CD4+T细胞的表达及意义[J].免疫学杂志,2014,30(7):612-616.
[22]刘瑞琪,于海涛,杨喜梅,等.芳香烃受体在SLE患者淋巴细胞中的变化及意义[J].免疫学杂志,2017,33(12):1047-1052.
[23]Schiering C,Wincent E,Metidji A,et al.Feedback control of AHR signalling regulates intestinal immunity[J].Nature,2017,542(7640):242-245.
[24]Singh NP,Singh UP,Rouse M,et al.Dietary indoles suppress delayed-type hypersensitivity by inducing a switch from proinflammatory Th17 cells to antiinflammatory regulatory T cells through regulation of microRNA[J].J Immunol,2016,196(3):1108-1122.
[25]Veldhoen M,Hirota K,Christensen J,et al.Natural agonists for aryl hydrocarbon receptor in culture medium are essential for optimal differentiation of Th17 T cells[J].JExp Med,2009,206(1):43-49.
[26]Qiu J,Heller JJ,Guo X,et al.The aryl hydrocarbon receptor regulates gut immunity through modulation of innate lymphoid cells[J].Immunity,2012,36(1):92-104.
[27]Winans B,Nagari A,Chae M,et al.Linking the aryl hydrocarbon receptor with altered DNA methylation patterns and developmentally induced aberrant antiviral CD8+T cell responses[J].J Immunol,2015,194(9):4446-4457.
[28]Cibrian D,Saiz ML,de la Fuente H,et al.CD69 controls the uptake of L-tryptophan through LAT1-CD98 and AhR-dependent secretion of IL-22 in psoriasis[J].Nat Immunol,2016,17(8):985-996.
[29]Sherr DH,Monti S.The role of the aryl hydrocarbon receptor in normal and malignant B cell development[J].Semin Immunopathol,2013,35(6):705-716.
[30]Suh J,Jeon YJ,Kim HM,et al.Aryl hydrocarbon receptordependent inhibition of AP-1 activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin in activated B cells[J].Toxicol Appl Pharmacol,2002,181(2):116-123.