GPR17 regulates immune pulmonary inflammation induced by house dust mites.
Antagonists of the type 1 cysteinyl leukotriene receptor (CysLT(1)R) are efficacious for bronchoconstriction in humans with bronchial asthma; however, the clinical response to these drugs is heterogeneous. In particular, how CysLT(1)R expression and function are constitutively regulated in vivo is not known. In this study, we show that a seven-transmembrane receptor, GPR17, negatively regulates the CysLT(1)R-mediated inflammatory cell accumulation in the bronchoalveolar lavage fluid and lung, the levels of IgE and specific IgG1 in serum, and Th2/Th17 cytokine expression in the lung after intranasal sensitization and challenge with the house dust mite (extract of Dermatophagoides farinae [Df]) in mice. Sensitization of naive wild-type recipients with Df-pulsed bone marrow-derived dendritic cells of each genotype or sensitization of each genotype with Df-pulsed wild-type bone marrow-derived dendritic cells and Df challenge revealed markedly increased pulmonary inflammatory and serum IgE responses for GPR17-deficient mice as compared with wild-type mice and reduced responses in the genotypes lacking CysLT(1)R. These findings reveal a constitutive negative regulation of CysLT(1)R functions by GPR17 in both the Ag presentation and downstream phases of allergic pulmonary inflammation.
Maekawa
Akiko
A
Department of Medicine, Harvard Medical School and Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA 02115, USA. amaekawa@rics.bwh.harvard.edu
Xing
Wei
W
Austen
K Frank
KF
Kanaoka
Yoshihide
Y
D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D040001:Dermatophagoides farinae / Q000276:immunology*; D003888:Desensitization, Immunologic; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D020381:Interleukin-17 / Q000096:biosynthesis / Q000235:genetics; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018077:Receptors, Leukotriene / Q000172:deficiency / Q000378:metabolism / Q000502:physiology; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000473:pathology* / Q000517:prevention & control; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D000485:Allergens; C534979:GPR17 protein, mouse; D007074:Immunoglobulin G; D020381:Interleukin-17; D009419:Nerve Tissue Proteins; D043562:Receptors, G-Protein-Coupled; D018077:Receptors, Leukotriene; D007073:Immunoglobulin E; C083169:leukotriene D4 receptor