科研之友
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摘要
The aryl hydrocarbon receptor (AHR) has garnered considerable attention as a modulator of CD4+ cell lineage development and function. It also regulates antiviral CD8+ T-cell responses, but via indirect mechanisms that have yet to be determined. Here, we show that during acute influenza virus infection, AHR activation skews dendritic-cell (DC) subsets in the lung-draining lymph nodes, such that there are fewer conventional CD103+DCs and CD11b+DCs. Sorting DC subsets reveals AHR activation reduces immunostimulatory function of CD103+DCs in the mediastinal lymph nodes, and decreases their frequency in the lung. DNA-binding domain Ahr mutants demonstrate that alterations in DC subsets require the ligand-activated AHR to contain its inherent DNA-binding domain. To evaluate the intrinsic role of AHR in DCs, conditional knockouts were created using Cre-LoxP technology, which revealed that AHR in CD11c+ cells plays a key role in controlling the acquisition of effector CD8+ Tcells in the infected lung. However, AHR within other leukocyte lineages contributes to diminished naive CD8+ T-cell activation in the draining lymphoid nodes. These findings indicate DCs are among the direct targets of AHR ligands in vivo, and AHR signaling modifies host responses to a common respiratory pathogen by affecting the complex interplay of multiple cell types.
- 出版日期2014-6
