P2Y2R deficiency attenuates experimental autoimmune uveitis development.
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 f...
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doaj-8cb303d96e21438aa5da4eba128166af2020-11-25T02:22:52ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01102e011651810.1371/journal.pone.0116518P2Y2R deficiency attenuates experimental autoimmune uveitis development.Lia Judice M RelvasMaya MakhoulRemi DewispelaereLaure CaspersDidier CommuniJean-Marie BoeynaemsBernard RobayeCatherine BruynsFrançois WillermainWe 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.http://europepmc.org/articles/PMC4334221?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lia Judice M Relvas Maya Makhoul Remi Dewispelaere Laure Caspers Didier Communi Jean-Marie Boeynaems Bernard Robaye Catherine Bruyns François Willermain |
spellingShingle |
Lia Judice M Relvas Maya Makhoul Remi Dewispelaere Laure Caspers Didier Communi Jean-Marie Boeynaems Bernard Robaye Catherine Bruyns François Willermain P2Y2R deficiency attenuates experimental autoimmune uveitis development. PLoS ONE |
author_facet |
Lia Judice M Relvas Maya Makhoul Remi Dewispelaere Laure Caspers Didier Communi Jean-Marie Boeynaems Bernard Robaye Catherine Bruyns François Willermain |
author_sort |
Lia Judice M Relvas |
title |
P2Y2R deficiency attenuates experimental autoimmune uveitis development. |
title_short |
P2Y2R deficiency attenuates experimental autoimmune uveitis development. |
title_full |
P2Y2R deficiency attenuates experimental autoimmune uveitis development. |
title_fullStr |
P2Y2R deficiency attenuates experimental autoimmune uveitis development. |
title_full_unstemmed |
P2Y2R deficiency attenuates experimental autoimmune uveitis development. |
title_sort |
p2y2r deficiency attenuates experimental autoimmune uveitis development. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2015-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC4334221?pdf=render |
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