Herbsttagung Programm & Abstracts - Deutsche Gesellschaft für ...

Attenuated allergic airway inflammation in Cd39 -/- mice
C. Korcan Ayata 1 , Tobias Müller 1 , Thorsten Dürk 1 , Melanie Grimm 1 , Kristin Baudiß 1 , Rodolfo Paula
Vieira 1 , Sanja Cicko 1 , Andreas Zech 1 , Stephan Sorichter 1 , Julie Pelletier 2 , Jean Sévigny 2,3 , Simon
Robson 3 and Marco Idzko 1
1 Department of Pneumology, University Medical Center, Freiburg, Germany. 2 Centre de recherche en
Rhumatologie et Immunologie, Centre Hospitalier Universitaire de Québec, Québec, QC, Canada.
3 Département de microbiologie-infectiologie et d’immunologie, Faculté de Médecine, Université Laval,
Québec, QC, Canada. 4 Transplant 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.
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