Research Papers: Immunology:

P2rx4 deficiency in mice alleviates allergen-induced airway inflammation

Andreas Zech, Benjamin Wiesler, Cemil Korcan Ayata, Tilmann Schlaich, Thorsten Dürk, Madelon Hoßfeld, Nicolas Ehrat, Sanja Cicko and Marco Idzko _

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Oncotarget. 2016; 7:80288-80297. https://doi.org/10.18632/oncotarget.13375

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Andreas Zech1,*, Benjamin Wiesler1,*, Cemil Korcan Ayata1, Tilmann Schlaich1, Thorsten Dürk1, Madelon Hoßfeld1, Nicolas Ehrat1, Sanja Cicko1 and Marco Idzko1

1 Department of Pneumology, University Medical Centre Freiburg, Germany

* These authors have contributed equally to this work

Correspondence to:

Marco Idzko, email:

Keywords: asthma, P2RX4, ATP, dendritic cells, IL-1ß, Immunology and Microbiology Section, Immune response, Immunity

Received: September 30, 2016 Accepted: November 09, 2016 Published: November 15, 2016


Compelling evidences point out a crucial role for extracellular nucleotides such as adenosine triphosphate (ATP) during inflammatory conditions. Once released into the extracellular space, ATP modulates migration, maturation and function of various inflammatory cells via activating of purinergic receptors of the P2Y- and P2X- family. P2RX4 is an ATP-guided ion channel expressed on structural cells such as alveolar epithelial and smooth muscle cells as well as inflammatory cells including macrophages, dendritic cells (DCs) and T cells. P2RX4 has been shown to interact with P2RX7 and promote NLRP3 inflammasome activation. Although P2RX7 has already been implicated in allergic asthma, the role of P2RX4 in airway inflammation has not been elucidated yet. Therefore, we used a selective pharmacological antagonist and genetic ablation to investigate the role of P2RX4 in an ovalbumin (OVA) driven model of allergen-induced airway inflammation (AAI). Both, P2RX4 antagonist 5-BDBD treatment and P2rx4 deficiency resulted in an alleviated broncho alveolar lavage fluid eosinophilia, peribronchial inflammation, Th2 cytokine production and bronchial hyperresponsiveness. Furthermore, P2rx4-deficient bone marrow derived DCs (BMDCs) showed a reduced IL-1ß production in response to ATP accompanied by a decreased P2rx7 expression and attenuated Th2 priming capacity compared to wild type (WT) BMDCs in vitro. Moreover, mice adoptively transferred with P2rx4-deficient BMDCs exhibit a diminished AAI in vivo. In conclusion our data suggests that P2RX4-signaling contributes to AAI pathogenesis by regulating DC mediated Th2 cell priming via modulating IL-1ß secretion and selective P2RX4-antagonists might be a new therapeutic option for allergic asthma.

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