Thursday, September 4, 2014
Allergens and the airway epithelium response: Gateway to allergic sensitization
Allergic sensitization to inhaled antigens is increasingly common; however, the mechanisms remain poorly understood. Lung epithelial cells, once thought to be merely a passive barrier impeding allergen penetrance, have recently been shown to recognize allergens via expression of pattern recognition receptors (PRRs) and mount an innate immune response driven by the activation of the cytokine NF-кB. In their review, Lambrecht and Hammad discuss recent findings that describe epithelial cells as crucial in allergy inhalation outcomes (J Allergy Clin Immunol 2014; 134(3): 499-507).
Traditionally, allergic asthma has been characterized as a disease of the adaptive immune system, whereby lymphocytes overreact to harmless antigens and mount a type 2 immune response, subsequently causing the activation of effector cells like mast cells, basophils and eosinophils. Recently, research has been changing this view to accommodate the concept that cells of the innate immune system contribute significantly to disease pathogenesis, by recognizing allergens and providing an early warning system of cytokine production and danger signals. The authors discuss the innate immune functions of barrier epithelial cells (AECs) of the airways as they respond to inhaled allergens in mouse models. Specifically, that AECs sense the presence of allergens and relay this information to airway dendritic cells (DCs), which are the most proficient antigen presenting cells of the lung that translate information received by epithelial cells which ultimately signals the T and B lymphocytes of the adaptive immune system. In response to allergen recognition, AECs also orchestrate the early recruitment and activation of type 2 innate lymphocytes (ILC2s), using the same activation signals that also activate DCs. In turn, this activation leads to the production of type 2 cytokines and thus the adaptive immune response.
Although it is now clear how AECs are activated to ultimately recruit and activate DCs leading to Th2 immunity in mouse models in response to allergen, it is unclear if this scheme is reproduced in humans, or if it is true for all allergens. The authors explain that we are only beginning to understand how genetics and environment influence the epithelia-DC crosstalk that leads to allergy and further research will expand how the AEC/DC/ILC2 interaction bridges innate and adaptive immunity at the origin of the allergic sensitization process.