Pneumologie 2013; 67 - V255
DOI: 10.1055/s-0033-1334687

Attenuated allergic airway inflammation in Cd39-/- mice

M Idzko 1, K Ayata 1, T Müller 1, T Dürk 1, M Grimm 1, K Baudiß 1, RP Vieira 1, S Cicko 1, A Zech 1, S Sorichter 1, J Pelletier 2, J Sévigny 3, S Robson 4
  • 1Department of Pneumology, University Medical Center, Freiburg
  • 2Centre de Recherche en Rhumatologie et Immunologie, Centre Hospitalier Universitaire de Québec, Qc, Canada
  • 3Département de Microbiologie-Infectiologie et d'immunologie, Faculté de Médecine, Université Laval, Québec, Qc, Canada
  • 4Transplant Institute and Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

Rationale: Extracellular ATP accumulates in the lung following allergen challenge and contributes, via activation of purinergic receptors on dendritic cells (DC), to the development of allergic airway inflammation (AAI). ATP-levels in the airways are normally tightly regulated by CD39 ectonucleotidase that is highly expressed in several tissues including skin and bone marrow DC. CD39 has been shown to modulate DC adaptive/haptenic immune responses.

Objectives: To evaluate the impact of altered purinergic signaling on myeloid DC on AAI using Cd39 deficient mice.

Methods: OVA-alum and house dust mite (HDM) bone marrow derived DC (BMDC) dependent models of allergic airway inflammation were studied in Cd39 deficient mice. Migration assays, time lapse microscopy and T-cell priming assays were used to determine functional relevance of CD39 expression on DC in the setting of Th2-mediated responses.

Results: Cd39 -/- mice exhibited marked increases in extracellular ATP levels in BALF but had paradoxically limited AAI in both OVA-alum and HDM models. These homeostatic abnormalities and associated purinergic desensitization responses were associated with decreased myeloid DC chemotaxis towards ATP. Cd39 -/- DCs had very limited capacity to prime Th2-response, which was accompanied with impaired ability to form stable immune synaptic interactions with OVA specific naïve T-cells.

Conclusions: In a DC-driven model of AAI, Cd39 deficient DCs exhibited a limited capacity to induce Th2 immunity in vivo. Our data demonstrate a role of CD39 in the regulation of AAI and possibly other allergic diseases.