GPR17 regulates immune pulmonary inflammation induced by house dust mites

A Maekawa, W Xing, KF Austen… - The Journal of …, 2010 - journals.aai.org
A Maekawa, W Xing, KF Austen, Y Kanaoka
The Journal of immunology, 2010journals.aai.org
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 …
Abstract
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.
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