The prostaglandin D2 receptor 2 pathway in asthma: a key player in airway inflammation

Asthma is characterised by chronic airway inflammation, airway obstruction and hyper-responsiveness. The inflammatory cascade in asthma comprises a complex interplay of genetic factors, the airway epithelium, and dysregulation of the immune response. Prostaglandin D-2 (PGD(2)) is a lipid mediator, predominantly released from mast cells, but also by other immune cells such as T(H)2 cells and dendritic cells, which plays a significant role in the pathophysiology of asthma. PGD(2) mainly exerts its biological functions via two G-protein-coupled receptors, the PGD(2) receptor 1 (DP1) and 2 (DP2). The DP2 receptor is mainly expressed by the key cells involved in type 2 immune responses, including T(H)2 cells, type 2 innate lymphoid cells and eosinophils. The DP2 receptor pathway is a novel and important therapeutic target for asthma, because increased PGD(2) production induces significant inflammatory cell chemotaxis and degranulation via its interaction with the DP2 receptor. This interaction has serious consequences in the pulmonary milieu, including the release of pro-inflammatory cytokines and harmful cationic proteases, leading to tissue remodelling, mucus production, structural damage, and compromised lung function. This review will discuss the importance of the DP2 receptor pathway and the current understanding of its role in asthma.