253:
Type 6 Purinergic Receptors (P2Y6) Homeostatic Regulation In Allergic Sensitization And Lung Inflammation
Saturday, March 3, 2018: 5:45 PM
S210C (Convention Center)
Jun Nagai, , , ,
RATIONALE: Type 6 purinergic (P2Y6) receptors are high affinity G protein-coupled receptors (GPCRs) for UDP and the recently identified PGE2-G. We found that P2Y6 receptors inhibit type 2 immunity in lung allergic inflammation by incompletely understood mechanisms. In this study, we sought to determine the importance of P2Y6receptors in controlling sensitization or challenge phase by deleting the p2ry6 allele before or after sensitization.

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.