The impact of the prostaglandin D₂ receptor 2 and its downstream effects on the pathophysiology of asthma

Abstract

Current research suggests that the prostaglandin D2 (PGD2) receptor 2 (DP2) is a principal regulator in the pathophysiology of asthma, because it stimulates and amplifies the inflammatory response in this condition. The DP2 receptor can be activated by both allergic and nonallergic stimuli, leading to several pro‐inflammatory events, including eosinophil activation and migration, release of the type 2 cytokines interleukin (IL)‐4, IL‐5 and IL‐13 from T helper 2 (Th2) cells and innate lymphoid cells type 2 (ILCs), and increased airway smooth muscle mass via recruitment of mesenchymal progenitors to the airway smooth muscle bundle. Activation of the DP2 receptor pathway has potential downstream effects on asthma pathophysiology, including on airway epithelial cells, mucus hypersecretion, and airway remodelling, and consequently might impact asthma symptoms and exacerbations. Given the broad distribution of DP2 receptors on immune and structural cells involved in asthma, this receptor is being explored as a novel therapeutic target.

The Biology of Prostaglandins and Their Role as a Target for Allergic Airway Disease Therapy

“…In the airways, DP1 is expressed in the nasal mucous-secreting goblet cells, nasal serous glands, vascular endothelium, DCs, T cells, basophils, and eosinophils [21]. DP2 expression has been observed in both hematopoietic cells such as T cells, ILC2s, mast cells, basophils, and eosinophils, as well as in structural cells such as epithelial cells and smooth muscle cells [22]. Stimulation of DP1 increases the intracellular cyclic adenosine 3 ,5 -monophosphate (cAMP) level, which is believed to inhibit target cell functions and suppress innate immune functions, for example the generation of inflammatory mediators.…”

Ramatroban as a Novel Immunotherapy for COVID-19

“…Studies over the past decade have investigated the role of PGD 2 in regulating the innate and adaptive immune responses to the SARS-CoV viruses. PGD 2 signals primarily through three G-protein coupled receptors, first the D-prostanoid receptor 1 (DP 1 ); second, prostanoid receptor 2 (DP 2 ) which was identified previously as the "chemoattractant receptor-homologous molecule expressed on Th2 cells" (CRTH2); and third, the thromboxane receptor (TP) [14,15]. PGD 2 effects on cellular elements in the respiratory tree including pulmonary capillary endothelial cells, airway epithelial cells and cells of the innate and adaptive immune system are diverse and cell specific [4].…”

Mucins and Asthma: Are We Headed to the Revolutionary Road?

“…Prostaglandin D2 (PDG2) contributes to T2 inflammation through binding to the G-protein-coupled receptor chemoattractant receptor-homologous molecule expressed on TH2 cells (CRTH2). The activation of this pathway has potent downstream effects including mucus hypersecretion and airway remodeling [10,11]. Fevipiprant is an oral competitive antagonist of CRTH2 and, together with the GB001 compound [12], is the most promising oral drug currently under investigation for patients with moderate to severe asthma and a T2 inflammatory profile [10,12].…”