CRTH2 (Chemoattractant Receptor-homologous molecule expressed on Th2 cells) is a G-protein coupled receptor expressed by Th2 lymphocytes, eosinophils, and basophils. The receptor mediates the activation and chemotaxis of these cell types in response to prostaglandin D2 (PGD2), the major prostanoid produced by mast cells.
PGD2 is released through mast cell degranulation in the initial phase of IgE-mediated reactions. This process is also thought to occur at the site of inflammation, such as the nasal and bronchial mucosa.
Through interaction with CRTH2, PGD2 is thought to mediate recruitment and activation of CRTH2-bearing cell types to the site of the allergic reaction, in consequence amplifying and maintaining the allergic inflammation. In the nasal and bronchial mucosa, this pro-inflammatory cascade is thought to start during the so-called late allergic response (LAR) occurring 3 to 9 hours after allergen challenge.
The interaction between PGD2 and CRTH2 would therefore contribute to the so-called “Th2 polarization”, with consequent Th2 cytokine production and the typical eosinophilic and basophilic characteristics of the inflammation.
Actelion believes that based on this information:
- CRTH2 antagonism has the potential to influence the allergic response at a high hierarchical level (Th2 cell)
- CRTH2 antagonism could have the potential to affect the LAR, as well as phases of the allergy-borne inflammation and its consequences beyond LAR
