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 D₂ (PGD₂) is a lipid mediator, predominantly released from mast cells, but also by other immune cells such as T_H2 cells and dendritic cells, which plays a significant role in the pathophysiology of asthma. PGD₂ mainly exerts its biological functions via two G-protein-coupled receptors, the PGD₂ receptor 1 (DP₁) and 2 (DP₂). The DP₂ receptor is mainly expressed by the key cells involved in type 2 immune responses, including T_H2 cells, type 2 innate lymphoid cells and eosinophils. The DP₂ receptor pathway is a novel and important therapeutic target for asthma, because increased PGD₂ 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.