METHODS: p2ry6(flox/flox);rosa26creER/+ and p2ry6(flox/flox);+/+ controls were treated with tamoxifen starting either before the initial sensitization, or immediately following the sensitization. The mice were sensitized with an extract from Dermatophagoides farinae intranasally on days 0-1 and challenged on days 14-15 separately.
RESULTS: Tamoxifen treatment for 5 days decreased the expression of P2Y6 in the lung, spleen and lymph node by ~90%. When P2Y6 receptors were deleted before sensitization, Df-treated p2ry6(flox/flox);cre/+ mice exhibited significantly increased eosinophil and neutrophil counts in the BAL fluids compared p2ry6(flox/flox);+/+ controls, as well as increased bronchovascular cellular infiltration. In addition, higher levels of expression of Th2 cytokines and IL-33 mRNA transcripts were present in the lungs of the p2ry6(flox/flox);cre/+ mice than in the lungs of the p2ry6(flox/flox);+/+ controls. However, deleting P2Y6 after the sensitization phase did not induce the exacerbated lung inflammation and the expression of Th2 cytokines and IL-33 in the lungs of the p2ry6(flox/flox);cre/+ mice tended to be lower than the p2ry6(flox/flox);+/+ controls.
CONCLUSIONS: P2Y6 receptors expression during the sensitization phase plays a critical role in preventing sensitization to the allergen. P2Y6 agonist might prove a new therapeutic approach to inhibit the allergic lung inflammation.