Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates the toxic activity of many environmental xenobiotics. However, its role in innate immune responses during viral infection is not fully understood. Here we demonstrate that constitutive AHR signaling negatively regulates the type I interferon (IFN-I) response during infection with various types of virus. Virus-induced IFN-β production was enhanced in AHR- IFN-I-mediated innate response and, further, suggests that the AHR-TIPARP axis is a potential therapeutic target for enhancing antiviral responses.AHR was originally discovered as a xenobiotic sensor that mediates the toxicity of the persistent environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), more commonly known as dioxin [1][2][3][4] . Activation of AHR induces its target genes, including those encoding cytochrome P4501A1, cytochrome P4501B1, AHR repressor, TCDD-inducible poly(ADP-ribose)polymerase (TIPARP) and aldehyde dehydrogenase 1A3 (refs. 1,2,5-9), which are involved in the adaptive metabolism of xenobiotic compounds. This property of AHR has been implicated in host defense against bacterial infection, as certain bacterial pigmented virulence factors are AHR agonists that are subsequently metabolized by AHR-regulated drug-metabolizing enzymes 10 . Studies of AHR-deficient mice have identified important physiological roles for AHR in response to endogenous ligands in cell cycle regulation, cell differentiation and immune responses 8,[11][12][13][14] . In relation to this, several putative endogenous ligands for the AHR have also been reported, including heme metabolites, arachidonic acids or leukotrienes and tryptophan metabolites, such as 6-formylindolo(3,2-b)carbazole (FICZ) and kynurenine (Kyn) 2,8,15 .There has been increased interest in understanding the role of AHR in immunity.Several reports, most of which are based mainly on experiments with dioxin treatment, have shown that the AHR is involved in the differentiation and/or function of T cells, macrophages and dendritic cells 7,9,11,[16][17][18][19][20][21] . AHR has been implicated in the control of acute graft-versus-host disease and autoimmunity 11,12,21 . Dioxin-activated AHR also reduces the survival rate of mice infected with influenza A virus 22,23 and indirectly suppresses the proliferation and differentiation of virus-specific CD8 + T cells via its regulatory role in dendritic cells 24 . FICZ and dioxin diminish CD8 + T cell responsiveness, whereas dioxin, but not FICZ, affects neutrophil recruitment or pulmonary inducible nitric oxide synthase (iNOS) induction in response to influenza virus infection 25 .Tryptophan metabolites such as Kyn are upregulated during inflammation and/or tumor progression in several types of immune and tumor cells through the catalytic activity of tryptophan dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO), which catalyze the first step in the formation of Kyn from tryptophan 2,9 . This increase in Kyn leads to an increase in regulatory T c...

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Background. Prediction and prevention of hepatitis B virus (HBV)-related

The response rates, median OS time and TTP in patients with advanced HCC with PVTT who received this novel combination therapy of intra-arterial 5-FU and subcutaneous IFN with IGRT are encouraging, and this combination therapy warrants further investigation.