title: The purinergic G protein-coupled receptor 6 inhibits effector T cell activation in allergic pulmonary inflammation.
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.
authors: Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
authors: Giorgio
authors: G
authors: Giannattasio
authors: Shin
authors: S
authors: Ohta
authors: Joshua R
authors: JR
authors: Boyce
authors: Wei
authors: W
authors: Xing
authors: Barbara
authors: B
authors: Balestrieri
authors: Joshua A
authors: JA
authors: Boyce
mesh_terms: D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000008:administration & dosage / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D007108:Immune Tolerance / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018048:Receptors, Purinergic P2 / Q000172:deficiency / Q000502:physiology*; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D000485:Allergens; D039741:Antigens, Dermatophagoides; D018048:Receptors, Purinergic P2; C099845:purinoceptor P2Y6