title: P2Y2R deficiency attenuates experimental autoimmune uveitis development.
abstract: We aimed to study the role of the nucleotide receptor P2Y2R in the development of experimental autoimmune uveitis (EAU). EAU was induced in P2Y2+/+ and P2Y2-/- mice by immunization with IRBP peptide or by adoptive transfer of in vitro restimulated semi-purified IRBP-specific enriched T lymphocytes from spleens and lymph nodes isolated from native C57Bl/6 or P2Y2+/+ and P2Y2-/- immunized mice. Clinical and histological scores were used to grade disease severity. Splenocytes and lymph node cell phenotypes were analyzed using flow cytometry. Semi-purified lymphocytes and MACS-purified CD4+ T lymphocytes from P2Y2+/+ and P2Y2-/- immunized mice were tested for proliferation and cytokine secretion. Our data show that clinical and histological scores were significantly decreased in IRBP-immunized P2Y2-/- mice as in P2Y2-/- mice adoptively transfered with enriched T lymphocytes from C57Bl/6 IRBP-immunized mice. In parallel, naïve C57Bl/6 mice adoptively transferred with T lymphocytes from P2Y2-/- IRBP-immunized mice also showed significantly less disease. No differences in term of spleen and lymph node cell recruitment or phenotype appeared between P2Y2-/- and P2Y2+/+ immunized mice. However, once restimulated in vitro with IRBP, P2Y2-/- T cells proliferate less and secrete less cytokines than the P2Y2+/+ one. We further found that antigen-presenting cells of P2Y2-/- immunized mice were responsible for this proliferation defect. Together our data show that P2Y2-/- mice are less susceptible to mount an autoimmune response against IRBP. Those results are in accordance with the danger model, which makes a link between autoreactive lymphocyte activation, cell migration and the release of danger signals such as extracellular nucleotides.
authors.affiliation: Dpt of Ophthalmology, CHU St-Pierre and Brugmann, Brussels, Belgium; The Institute of Interdisciplinary Research, IRIBHM, Brussels, Belgium; Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Lia Judice M
authors.initials: LJ
authors.lastname: Relvas
authors.affiliation: The Institute of Interdisciplinary Research, IRIBHM, Brussels, Belgium; Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Maya
authors.initials: M
authors.lastname: Makhoul
authors.affiliation: Dpt of Ophthalmology, CHU St-Pierre and Brugmann, Brussels, Belgium; The Institute of Interdisciplinary Research, IRIBHM, Brussels, Belgium; Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Remi
authors.initials: R
authors.lastname: Dewispelaere
authors.affiliation: Dpt of Ophthalmology, CHU St-Pierre and Brugmann, Brussels, Belgium; Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Laure
authors.initials: L
authors.lastname: Caspers
authors.affiliation: The Institute of Interdisciplinary Research, IRIBHM, Brussels, Belgium; Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Didier
authors.initials: D
authors.lastname: Communi
authors.affiliation: The Institute of Interdisciplinary Research, IRIBHM, Brussels, Belgium; Dpt of Laboratory Medicine, Erasme Hospital, Brussels, Belgium; Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Boeynaems
authors.affiliation: The Institute of Interdisciplinary Research, IRIBHM, Gosselies, Belgium; Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Bernard
authors.initials: B
authors.lastname: Robaye
authors.affiliation: The Institute of Interdisciplinary Research, IRIBHM, Brussels, Belgium; Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Catherine
authors.initials: C
authors.lastname: Bruyns
authors.affiliation: Dpt of Ophthalmology, CHU St-Pierre and Brugmann, Brussels, Belgium; The Institute of Interdisciplinary Research, IRIBHM, Brussels, Belgium; Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: François
authors.initials: F
authors.lastname: Willermain
mesh_terms: D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology* / Q000378:metabolism*; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D005136:Eye Proteins / Q000737:chemistry; D055786:Gene Knockout Techniques; D006801:Humans; D007114:Immunization; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D058473:Receptors, Purinergic P2Y2 / Q000172:deficiency* / Q000235:genetics; D012177:Retinol-Binding Proteins / Q000737:chemistry; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014605:Uveitis / Q000276:immunology* / Q000378:metabolism*; D000099214:Retinol-Binding Proteins, Interstitial
chemical_list: D016207:Cytokines; D005136:Eye Proteins; D010446:Peptide Fragments; D058473:Receptors, Purinergic P2Y2; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial