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Late-breaking abstract: Critical role of proton-sensing OGR1 in dendritic cells in development of asthma

Haruka Aoki, Takeshi Hisada, Chihiro Mogi, Masakiyo Yatomi, Hiroaki Tsurumaki, Yosuke Kamide, Akihiro Ono, Yasuhiko Koga, Kunio Dobashi, Tamotsu Ishizuka, Masanobu Yamada, Fumikazu Okajima
European Respiratory Journal 2014 44: P1804; DOI:
Haruka Aoki
1Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan
2Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan
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Takeshi Hisada
2Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan
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Chihiro Mogi
1Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan
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Masakiyo Yatomi
1Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan
2Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan
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Hiroaki Tsurumaki
1Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan
2Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan
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Yosuke Kamide
2Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan
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Akihiro Ono
2Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan
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Yasuhiko Koga
2Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan
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Kunio Dobashi
3School of Health Sciences, Gunma University, Maebashi, Japan
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Tamotsu Ishizuka
4Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
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Masanobu Yamada
2Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan
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Fumikazu Okajima
1Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan
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Abstract

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.

  • Asthma - mechanism
  • Allergy
  • Immunology
  • © 2014 ERS
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Late-breaking abstract: Critical role of proton-sensing OGR1 in dendritic cells in development of asthma
Haruka Aoki, Takeshi Hisada, Chihiro Mogi, Masakiyo Yatomi, Hiroaki Tsurumaki, Yosuke Kamide, Akihiro Ono, Yasuhiko Koga, Kunio Dobashi, Tamotsu Ishizuka, Masanobu Yamada, Fumikazu Okajima
European Respiratory Journal Sep 2014, 44 (Suppl 58) P1804;

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Late-breaking abstract: Critical role of proton-sensing OGR1 in dendritic cells in development of asthma
Haruka Aoki, Takeshi Hisada, Chihiro Mogi, Masakiyo Yatomi, Hiroaki Tsurumaki, Yosuke Kamide, Akihiro Ono, Yasuhiko Koga, Kunio Dobashi, Tamotsu Ishizuka, Masanobu Yamada, Fumikazu Okajima
European Respiratory Journal Sep 2014, 44 (Suppl 58) P1804;
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