The roles of the prostaglandin D₂ receptors DP₁ and CRTH2 in promoting allergic responses

Prostaglandin D₂ (PGD₂) is produced by mast cells, Th2 lymphocytes and dendritic cells and has been detected in high concentrations at sites of allergic inflammation. PGD₂ exerts its inflammatory effects through high affinity interactions with the G protein coupled receptors DP₁ and chemoattractant-homologous receptor expressed on Th2 cells (CRTH2, also known as DP₂). DP₁ and CRTH2 act in concert to promote a number of biological effects associated with the development and maintenance of the allergic response. During the process of allergen sensitization, DP₁ activation may enhance polarization of Th0 cells to Th2 cells by inhibiting production of interleukin 12 by dendritic cells. Upon exposure to allergen in sensitized individuals, activation of DP₁ may contribute to the long lasting blood flow changes in the target organ. CRTH2 is expressed by Th2 lymphocytes, eosinophils and basophils and may mediate the recruitment of these cell types during the late phase allergic response. The role played by CRTH2 in promoting the production of Th2 cytokines and IgE make antagonism of this receptor a particularly attractive approach to the treatment of chronic allergic disease.

British Journal of Pharmacology (2008) 153, S191–S199; doi:10.1038/sj.bjp.0707488; published online 29 October 2007