THE P2Y6 RECEPTOR INHIBITS EFFECTOR T CELL ACTIVATION IN ALLERGIC PULMONARY INFLAMMATION
Giannattasio, Giorgio (2010) THE P2Y6 RECEPTOR INHIBITS EFFECTOR T CELL ACTIVATION IN ALLERGIC PULMONARY INFLAMMATION. [Tesi di dottorato] (Inedito)
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We show that the P2Y6 receptor, a G-protein-coupled receptor with high affinity for the nucleotide uridine diphosphate, is an important endogenous inhibitor of T cell function in allergic pulmonary inflammation. Mice conditionally deficient in P2Y6 receptors [p2ry6 (flox/flox);cre/+ mice] exhibited severe airway and tissue pathology relative to P2Y6-sufficient [p2ry6 (flox/flox)] littermates (+/+ mice) when treated intranasally with an extract (Df) of the dust mite Dermatophagoides farinae. P2Y6 receptors were inducibly expressed by lung, lymph node and splenic CD4+ and CD8+ T cells of Df-treated +/+ mice. Df-restimulated P2Y6-deficient lymph node cells produced higher levels of Th1 and Th2 cytokines, and polyclonally-stimulated P2Y6-deficient CD4+ T cells proliferated faster than comparably stimulated P2Y6-sufficient cells. The absence of P2Y6 receptors on CD4+ cells, but not antigen presenting cells, was sufficient to amplify cytokine generation. Thus, P2Y6 receptors protect the lung against exuberant allergen-induced pulmonary inflammation by inhibiting the activation of effector T cells.
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