The role of dendritic cells in immune regulation and allergic airway inflammation

Dendritic cells (DC) are potent antigen presenting cells that display an extraordinary capacity to present antigen to naïve T-cells and initiate primary immune responses. In the context of the lung and upper airway it is clear that DC play a key role in the regulation of adaptive immune responses to inhaled antigen. DC are particularly sensitive to signals derived from microbes, allergens and the airway tissue microenvironment. By the nature of the signals they provide at the time of antigen presentation, DC can polarize naïve T-cells into either T-helper type 1 (Th1) or Th2 effector cells, and are increasingly recognized as having a central role in the establishment of T-cell memory and peripheral immune tolerance. DC form a network within the upper airway and lung, and are rapidly recruited from the circulation in response to a variety of proinflammatory stimuli. Studies using animal models have highlighted the role of DC in both the initiation and maintenance of allergic airway inflammation. In early childhood, human DC are functionally immature, and this is thought to contribute to the development of allergic sensitization in those children who are genetically at risk for the development of atopy. Increased numbers of airway mucosal DC are found in both allergic rhinitis and asthma, while studies of blood-derived DC have emphasized important differences between the function of DC from atopic and normal individuals. This article reviews recent information on the involvement of DC in allergic airway disease, and the mechanisms by which DC could be exploited as targets for therapy in asthma and allergic rhinitis.