Epithelial, dendritic, and CD4+ T cell regulation of and by reactive oxygen and nitrogen species in allergic sensitization

BackgroundWhile many of the contributing cell types and mediators of allergic asthma are known, less well understood are the factors that induce allergy in the first place. Amongst the mediators speculated to affect initial allergen sensitization and the development of pathogenic allergic responses to innocuous inhaled antigens and allergens are exogenously or endogenously generated reactive oxygen species (ROS) and reactive nitrogen species (RNS).Scope of reviewThe interactions between ROS/RNS, dendritic cells (DCs), and CD4+ T cells, as well as their modulation by lung epithelium, are of critical importance for the genesis of allergies that later manifest in allergic asthma. Therefore, this review will primarily focus on the initiation of pulmonary allergies and the role that ROS/RNS may play in the steps therein, using examples from our own work on the roles of NO2 exposure and airway epithelial NF-κB activation.Major conclusionsEndogenously generated ROS/RNS and those encountered from environmental sources interact with epithelium, DCs, and CD4+ T cells to orchestrate allergic sensitization through modulation of the activities of each of these cell types, which quantitiatively and qualitatively dictate the degree and type of the allergic asthma phenotype.General significanceKnowledge of the effects of ROS/RNS at the molecular and cellular levels has the potential to provide powerful insight into the balance between inhalational tolerance (the typical immunologic response to an innocuous inhaled antigen) and allergy, as well as to potentially provide mechanistic targets for the prevention and treatment of asthma.

Research highlights
► Reactive oxygen species (ROS) and reactive nitrogen species (RNS) affect allergic sensitization.
► The lung is exposed to environmental and endogenously generated ROS and RNS.
► Epithelial, dendritic, and CD4+ T cells are targets and generators of ROS and RNS.
► The NF-kappaB (NF-κB) pathway is an especially important intracellular target of ROS and RNS.
► Airway epithelial NF-κB activity modulates allergic sensitization.