Aquaporin 9 regulates mast cell activation

Mast cells regulate immune responses in part through the release of granules containing mediators, such as histamine, cytokines and proteases. Cross-linking of IgE on FcεRI by antigen results in mast cell activation, a hallmark of allergy and anaphylaxis. Mechanisms that inhibit the activation of these cells might provide novel therapeutic approaches. Using a microarray expression approach, we identified a water channel, Aquaporin 9, that is highly expressed by mast cells, but its role on these cells remained unclear. To investigate this, mast cells were studied after treatment with phloretin, a highly specific chemical inhibitor of Aquaporin 9. Mast cells activated in the presence of phloretin showed significant down-regulation of several cytokines induced by activation, including IL-4, IL-5, IL-6, IL-13 and IL-33. Similarly, degranulation and cell migration were significantly reduced in a dose-dependent manner. Our data suggests that Aquaporin 9 is necessary for mast cell activation and could be a novel target for the treatment of allergies.