Differential Modulation of Dendritic Cell Biology by Endogenous and Exogenous Aryl Hydrocarbon Receptor Ligands

被引:5
作者
Sadeghi Shermeh, Atefeh [1 ]
Royzman, Dmytro [1 ]
Kuhnt, Christine [1 ]
Drassner, Christina [1 ]
Stich, Lena [1 ]
Steinkasserer, Alexander [1 ]
Knippertz, Ilka [1 ]
Wild, Andreas B. [1 ]
机构
[1] Friedrich Alexander Univ Erlangen Nurnberg, Dept Immune Modulat, Univ Klinikum Erlangen, D-91052 Erlangen, Germany
关键词
aryl hydrocarbon receptor; dendritic cells; exogenous ligands; endogenous ligands; POLYCYCLIC AROMATIC-HYDROCARBONS; FUNCTIONAL-DIFFERENTIATION; ACTIVATION; CONSEQUENCES; MECHANISMS; EXPRESSION; MATURATION; INDUCTION; CD25;
D O I
10.3390/ijms24097801
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The aryl hydrocarbon receptor (AhR) is a decisive regulatory ligand-dependent transcription factor. It binds highly diverse ligands, which can be categorized as either endogenous or exogenous. Ligand binding activates AhR, which can adjust inflammatory responses by modulating immune cells such as dendritic cells (DCs). However, how different AhR ligand classes impact the phenotype and function of human monocyte-derived DCs (hMoDCs) has not been extensively studied in a comparative manner. We, therefore, tested the effect of the representative compounds Benzo(a)pyrene (BP), 6-formylindolo[3,2-b]carbazole (FICZ), and Indoxyl 3-sulfate (I3S) on DC biology. Thereby, we reveal that BP significantly induces a tolerogenic response in lipopolysaccharide-matured DCs, which is not apparent to the same extent when using FICZ or I3S. While all three ligand classes activate AhR-dependent pathways, BP especially induces the expression of negative immune regulators, and subsequently strongly subverts the T cell stimulatory capacity of DCs. Using the CRISPR/Cas9 strategy we also prove that the regulatory effect of BP is strictly AhR-dependent. These findings imply that AhR ligands contribute differently to DC responses and incite further studies to uncover the mechanisms and molecules which are involved in the induction of different phenotypes and functions in DCs upon AhR activation.
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页数:20
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