Prostaglandin D2 pathway (PGD2 pathway)

The Prostaglandin D2 (PGD2) pathway is a lipid-mediated signaling cascade that plays a central role in the orchestration of allergic inflammation and type 2 immune responses [2, 3]. PGD2 is synthesized from arachidonic acid via the cyclooxygenase (COX) pathway and subsequent action of PGD synthases, notably the hematopoietic (H-PGDS) and lipocalin-type (L-PTGDS) isoforms [1, 10]. It acts primarily through two G protein-coupled receptors: DP1 (PTGDR) and DP2 (CRTH2/PTGDR2) [6, 11]. While DP1 is involved in vasodilation and some anti-inflammatory processes, DP2 is a key driver of the recruitment and activation of Th2 lymphocytes, eosinophils, and basophils [4, 6]. This pathway is heavily implicated in the pathogenesis of asthma, allergic rhinitis, and androgenetic alopecia, where elevated PGD2 levels correlate with disease severity [5, 8]. Pharmacological intervention typically involves DP2 receptor antagonists or H-PGDS inhibitors, aimed at dampening the inflammatory cascade [3, 9]. Despite significant clinical interest, several high-profile DP2 antagonists have faced challenges in demonstrating robust efficacy in broad patient populations, highlighting the need for precise patient stratification [6, 12].

Other names

PGD2 signalingProstaglandin D2 signaling cascadePGD2/DP1/DP2 axis

Antagonism of the Prostaglandin D2 receptor 1 (DP1) and Prostaglandin D2 receptor 2 (DP2/CRTH2); Inhibition of hematopoietic prostaglandin D2 synthase (H-PGDS) [3, 9, 11].