Late-Breaking Abstract: Critical Role of Proton Sensing Ogr1 in Dendritic Cells in Development of Asthma

Background: Ovarian cancer G protein-coupled receptor 1 (OGR1) stimulation by extracellular protons causes the activation of G proteins and subsequent cellular functions. However, the physiological and pathophysiological roles of OGR1 in airway responses remain largely unknown. Objective: We examined whether OGR1 is involved in the asthmatic inflammatory responses. Methods: Mice deficient in OGR1 were sensitized and challenged with ovalbumin (OVA) to measure airway inflammation and hyperresponsiveness. To examine the involvement of dendritic cells (DCs) in the airway responses, OVA-pulsed bone marrow-derived DCs were intratracheally transferred. Functional OGR1 expression and its activities in relation to migration in DCs were examined in vitro . Results: OGR1-deficient mice are resistant to the cardinal features of asthma, including airway eosinophilia, bronchial hyperresponsiveness, and goblet cell metaplasia, in association with a remarkable inhibition of TH2 cytokine production, in an OVA-induced asthma model. Intratracheal transfer of OVA-primed bone marrow-derived DCs from OGR1-deficient mice to wild-type (WT) mice developed lower airway hyperresponsiveness and eosinophilia after OVA inhalation compared with the transfer of those from WT mice. The presence of functional OGR1 in DCs was confirmed by the expression of OGR1 mRNA and OGR1-dependent Ca2+ response. Migration of OVA-sensitized DCs was attenuated by OGR1 deficiency in an in vitro Transwell assay and an in vivo footpad assay. Conclusion: OGR1 in DCs is critical for TH2 phenotype modulation and subsequent induction of airway inflammation and hyperresponsiveness.