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Cutting Edge: Chemoattractant Receptor-Homologous Molecule Expressed on TH2 Cells Plays a Restricting Role on IL-5 Production and Eosinophil Recruitment

Eric Chevalier, Jeff Stock, Tim Fisher^*, Mathieu Dupont, Magali Fric, Helene Fargeau, Murielle Leport, Sylvain Soler, Schmidlin Fabien, Marie-Pierre Pruniaux, Michel Fink, Claude P. Bertrand, John McNeish and Baiyong Li^1,*

^* Department of Antibacterials, Immunology and Cancer and Department of Genomics and Proteomics Sciences, Pfizer Global Research and Development, Groton, CT 06340; and Department of Biology, Pfizer Global Research and Development, Fresnes, France

PGs play key regulatory roles in inflammation and immunity. PGD₂, released from mast cells and Th2 cells during allergic responses, has recently been shown to target a novel receptor, chemoattractant receptor-homologous molecule expressed TH2 cells (CRTH2), in addition to the classic PGD (DP) receptor. CRTH2 is expressed on Th2 cells and eosinophils and mediates chemotaxis of these cells to PGD₂. Thus, CRTH2 is thought to be a key receptor mediating eosinophil and Th2 cell recruitment during allergic responses. To examine the role of CRTH2 in this context in vivo, we generated CRTH2 knockout mice. Surprisingly, in an allergic inflammatory model of asthma, CRTH2 knockout mice showed enhanced eosinophil recruitment into the lung compared with wild-type littermate mice. This is consistent with our observation that CRTH2 knockout cells produce significantly higher amounts of IL-5 and IL-3 in vitro. These results suggest a nonredundant role of CRTH2 in restricting eosinophilia and allergic response in vivo.

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