The transcription factor AhR modulates the balance of functionally distinct DC subsets during influenza virus infection (106.5)

Abstract

Abstract The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor expressed in cells of the immune system. AhR activation by high-affinity ligands such as the pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin) has been shown to suppress immune responses and impair host resistance to infection. However, the mechanisms by which AhR activation modulates immune function remain poorly understood. Dendritic cells (DCs) are antigen-presenting cells (APCs) that play a key role in priming naïve T cells. We previously reported that AhR activation reduces the ability of DCs to prime influenza virus-specific naïve CD8+ T cells ex vivo. In this study, we show that AhR activation changes the number of functionally distinct DC subsets in the lung and mediastinal lymph nodes in influenza virus-infected mice. By adoptively transferring virus-specific naïve CD8+ T cells into recipient mice, we demonstrate that AhR activation in the recipients dramatically reduces the clonal expansion and differentiation of transferred naïve virus-specific CD8+ T cells. Moreover, using AhR mutant mice, which express an AhR protein that binds ligand but cannot interact directly with DNA, we found that alterations in DC phenotype require the ligand-activated AhR complex to bind DNA via AhR’s DNA binding domain. Our findings suggest that AhR activation modulates phenotypically-distinct DC subsets, which may contribute to altered susceptibility and response to respiratory viral infection.