DP2

DP2, also known as CRTH2 (chemoattractant receptor-homologous molecule expressed on T helper 2 cells) or GPR44, is a G protein-coupled receptor that binds prostaglandin D2 (PGD2). In humans it is encoded by the PTGDR2 gene and is part of the prostanoid receptor family, distinct from the DP1 receptor (PTGDR1). DP2 is expressed on several immune cell types, including Th2 cells, eosinophils, basophils, mast cells, and some innate lymphoid cells.

When PGD2 binds DP2, the receptor primarily couples to Gi proteins, leading to reduced intracellular cAMP and activation of downstream signaling pathways such as MAP kinases. This signaling promotes chemotaxis and activation of Th2 cells and recruits eosinophils and basophils to sites of inflammation, contributing to allergic inflammation and airway hyperresponsiveness. DP2 signaling supports the production of Th2 cytokines such as IL-4, IL-5, and IL-13, reinforcing type 2 immune responses.

Clinical relevance for DP2 centers on its role in allergic diseases. DP2 is implicated in asthma, allergic rhinitis, and atopic dermatitis, where PGD2-driven recruitment and activation of Th2-type cells contribute to symptoms. Because of its involvement in type 2 inflammation, DP2 has been investigated as a therapeutic target; several DP2 antagonists, including small molecules and antibodies, have entered preclinical and clinical trials. Results have been mixed, and no DP2-targeted therapy has become standard care. Ongoing research aims to identify patient subgroups most likely to benefit and to optimize combination strategies with other anti-inflammatory treatments.