Effect Of P2Y2 Deficiency On Experimental Autoimmune Uveitis Development

Abstract

Purpose: : To study the potential role of the nucleotide receptor P2Y2 in the development of experimental autoimmune uveitis (EAU).

Methods: : EAU were induced in WT and P2Y2 KO mice by direct immunization with IRBP peptide 1-20 or adoptive transfer of in vitro restimulated semi-purified lymphocytes from spleen and draining lymph nodes isolated from immunized mice. Clinical and histological scores were used to grade disease severity. Lymphocyte proliferation was measured by thymidine incorporation and cytokine secretion by ELISA. Flow cytometry was used to analyze cell surface marker expression.

Results: : EAU clinical scores were slightly decreased in KO mice. Similarly, adoptive transfer of semi-purified lymphocytes from KO into C57Bl/6 WT mice induced significantly less disease than the transfer of WT cells into C57Bl/6 WT animals. Analysis of spleen and lymph node cells of immunized animals showed no differences in term of cell populations. However, in vitro restimulation of KO cell induced less proliferation and cytokine (IFN gamma, TNF alpha and IL-17) secretion as compared to WT cells.

Conclusions: : Our data show that P2Y2 mice are less susceptible to develop an autoimmune response against IRBP peptide 1-20, influencing the development of EAU. Those data are consistent with the hypothesis that P2Y2 play a role of danger signal receptors.

Keywords: uveitis-clinical/animal model • inflammation