The plasmacytoid dendritic cell: at the cross-roads in asthma.

Jason P Lynch, Stuart B Mazzone, Matthew J Rogers, Jaisy J Arikkatt, Zhixuan Loh, Antonia L Pritchard, John W Upham, Simon Phipps

The onset, progression and exacerbations of asthma are frequently associated with viral infections of the lower respiratory tract. An emerging paradigm suggests that this relationship may be underpinned by a defect in the host's antiviral response, typified by the impaired production of type I and type III interferons (IFNs). The failure to control viral burden probably causes damage to the lung architecture and contributes to an aberrant immune response, which together compromise lung function. Although a relatively rare cell type, the plasmacytoid dendritic cell dedicates much of its transcriptome to the synthesis of IFNs and is pre-armed with virus-sensing pattern recognition receptors. Thus, plasmacytoid dendritic cells are specialised to ensure early viral detection and the rapid induction of the antiviral state to block viral replication and spread. In addition, plasmacytoid dendritic cells can limit immunopathology, and promote peripheral tolerance to prevent allergic sensitisation to harmless antigens, possibly through the induction of regulatory T-cells. Thus, this enigmatic cell may lie at an important intersection, orchestrating the immediate phase of antiviral immunity to effect viral clearance while regulating tolerance. Here, we review the evidence to support the hypothesis that a primary defect in plasmacytoid dendritic function may underlie the development of asthma.