title: The prostaglandin D₂ receptor CRTH2 regulates accumulation of group 2 innate lymphoid cells in the inflamed lung.
abstract: Group 2 innate lymphoid cells (ILC2s) promote type 2 cytokine-dependent immunity, inflammation, and tissue repair. Although epithelial cell-derived cytokines regulate ILC2 effector functions, the pathways that control the in vivo migration of ILC2s into inflamed tissues remain poorly understood. Here, we provide the first demonstration that expression of the prostaglandin D2 (PGD2) receptor CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells) regulates the in vivo accumulation of ILC2s in the lung. Although a significant proportion of ILC2s isolated from healthy human peripheral blood expressed CRTH2, a smaller proportion of ILC2s isolated from nondiseased human lung expressed CRTH2, suggesting that dynamic regulation of CRTH2 expression might be associated with the migration of ILC2s into tissues. Consistent with this, murine ILC2s expressed CRTH2, migrated toward PGD2 in vitro, and accumulated in the lung in response to PGD2 in vivo. Furthermore, mice deficient in CRTH2 exhibited reduced ILC2 responses and inflammation in a murine model of helminth-induced pulmonary type 2 inflammation. Critically, adoptive transfer of CRTH2-sufficient ILC2s restored pulmonary inflammation in CRTH2-deficient mice. Together, these data identify a role for the PGD2-CRTH2 pathway in regulating the in vivo accumulation of ILC2s and the development of type 2 inflammation in the lung.
authors: Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medical College, Cornell University, New York, New York, USA.|Institute for Immunology and Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors: E D Tait
authors: ED
authors: Wojno
authors: Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medical College, Cornell University, New York, New York, USA.
authors: L A
authors: LA
authors: Monticelli
authors: Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medical College, Cornell University, New York, New York, USA.
authors: S V
authors: SV
authors: Tran
authors: Institute for Immunology and Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors: T
authors: T
authors: Alenghat
authors: Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medical College, Cornell University, New York, New York, USA.
authors: L C
authors: LC
authors: Osborne
authors: Columbia Center for Translational Immunology and Department of Microbiology and Immunology, Columbia University Medical Center, New York, New York, USA.
authors: J J
authors: JJ
authors: Thome
authors: Department of Inflammation Research, Amgen, Seattle, Washington, USA.
authors: C
authors: C
authors: Willis
authors: Department of Inflammation Research, Amgen, Seattle, Washington, USA.
authors: A
authors: A
authors: Budelsky
authors: Columbia Center for Translational Immunology and Department of Microbiology and Immunology, Columbia University Medical Center, New York, New York, USA.|Department of Surgery, Columbia University Medical Center, New York, New York, USA.
authors: D L
authors: DL
authors: Farber
authors: Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medical College, Cornell University, New York, New York, USA.
authors: D
authors: D
authors: Artis
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002469:Cell Separation; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011014:Pneumonia / Q000276:immunology* / Q000378:metabolism; D015230:Prostaglandin D2 / Q000276:immunology* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D011971:Receptors, Immunologic / Q000276:immunology* / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000276:immunology* / Q000378:metabolism
chemical_list: D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor