title: Cutting edge: chemoattractant receptor-homologous molecule expressed on Th2 cells plays a restricting role on IL-5 production and eosinophil recruitment.
abstract: 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.
authors.affiliation: Department of Biology, Pfizer Global Research and Development, Fresnes, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Chevalier
authors.forename: Jeff
authors.initials: J
authors.lastname: Stock
authors.forename: Tim
authors.initials: T
authors.lastname: Fisher
authors.forename: Mathieu
authors.initials: M
authors.lastname: Dupont
authors.forename: Magali
authors.initials: M
authors.lastname: Fric
authors.forename: Helene
authors.initials: H
authors.lastname: Fargeau
authors.forename: Murielle
authors.initials: M
authors.lastname: Leport
authors.forename: Sylvain
authors.initials: S
authors.lastname: Soler
authors.forename: Schmidlin
authors.initials: S
authors.lastname: Fabien
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Pruniaux
authors.forename: Michel
authors.initials: M
authors.lastname: Fink
authors.forename: Claude P
authors.initials: CP
authors.lastname: Bertrand
authors.forename: John
authors.initials: J
authors.lastname: McNeish
authors.forename: Baiyong
authors.initials: B
authors.lastname: Li
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology*; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D004802:Eosinophilia / Q000235:genetics / Q000276:immunology; D004804:Eosinophils / Q000166:cytology / Q000276:immunology*; D005260:Female; D015848:Interleukin-5 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015230:Prostaglandin D2 / Q000378:metabolism / Q000502:physiology; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
chemical_list: D015848:Interleukin-5; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor