The purinergic G protein-coupled receptor 6 inhibits effector T cell activation in allergic pulmonary inflammation
G Giannattasio, S Ohta, JR Boyce, W Xing… - The Journal of …, 2011 - journals.aai.org
G Giannattasio, S Ohta, JR Boyce, W Xing, B Balestrieri, JA Boyce
The Journal of Immunology, 2011•journals.aai.orgWe show that the P2Y 6 receptor, a purinergic G protein-coupled receptor with a high affinity
for the nucleotide uridine diphosphate, is an important endogenous inhibitor of T cell
function in allergic pulmonary inflammation. Mice conditionally deficient in P2Y 6 receptors
[p2ry6 (flox/flox); cre/+ mice] exhibited severe airway and tissue pathology relative to P2Y 6-
sufficient [p2ry6 (flox/flox)] littermates (+/+ mice) when treated intranasally with an extract of
the dust mite Dermatophagoides farinae (Df). P2Y 6 receptors were inducibly expressed by …
for the nucleotide uridine diphosphate, is an important endogenous inhibitor of T cell
function in allergic pulmonary inflammation. Mice conditionally deficient in P2Y 6 receptors
[p2ry6 (flox/flox); cre/+ mice] exhibited severe airway and tissue pathology relative to P2Y 6-
sufficient [p2ry6 (flox/flox)] littermates (+/+ mice) when treated intranasally with an extract of
the dust mite Dermatophagoides farinae (Df). P2Y 6 receptors were inducibly expressed by …
Abstract
We show that the P2Y 6 receptor, a purinergic G protein-coupled receptor with a high affinity for the nucleotide uridine diphosphate, is an important endogenous inhibitor of T cell function in allergic pulmonary inflammation. Mice conditionally deficient in P2Y 6 receptors [p2ry6 (flox/flox); cre/+ mice] exhibited severe airway and tissue pathology relative to P2Y 6-sufficient [p2ry6 (flox/flox)] littermates (+/+ mice) when treated intranasally with an extract of the dust mite Dermatophagoides farinae (Df). P2Y 6 receptors were inducibly expressed by lung, lymph node, and splenic CD4+ and CD8+ T cells of Df-treated+/+ mice. Df-restimulated P2Y 6-deficient lymph node cells produced higher levels of Th1 and Th2 cytokines, and polyclonally stimulated P2Y 6-deficient CD4+ T cells proliferated faster than comparably stimulated P2Y 6-sufficient cells. The absence of P2Y 6 receptors on CD4+ cells, but not APCs, was sufficient to amplify cytokine generation. Thus, P2Y 6 receptors protect the lung against exuberant allergen-induced pulmonary inflammation by inhibiting the activation of effector T cells.
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