P2Y2R Deficiency Attenuates Experimental Autoimmune Uveitis Development |
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Authors: | Lia Judice M Relvas Maya Makhoul Remi Dewispelaere Laure Caspers Didier Communi Jean-Marie Boeynaems Bernard Robaye Catherine Bruyns Fran?ois Willermain |
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Institution: | 1Dpt of Ophthalmology, CHU St-Pierre and Brugmann, Brussels, Belgium;2The Institute of Interdisciplinary Research, IRIBHM, Brussels, Belgium;3The Institute of Interdisciplinary Research, IRIBHM, Gosselies, Belgium;4Dpt of Laboratory Medicine, Erasme Hospital, Brussels, Belgium;5Université Libre de Bruxelles, Brussels, Belgium;Boston University School of Medicine, UNITED STATES |
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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. |
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