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Updated: May 20, 2025
Experimental Autoimmune Uveitis: An Intraocular Inflammatory Mouse Model
Published on: January 12, 2022
Mice deficient of G-protein coupled receptor 3 (GPR3) developed severe experimental autoimmune uveitis (EAU) through
Nu Chen1, Jun Wu1, Deming Sun2
1Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville, School of Medicine, Louisville, KY, United States.
We discovered a protective role of G protein-coupled receptor 3 (GPR3) in a mouse model of T cell-mediated autoimmune uveitis. GPR3 is an orphan receptor that maintains Gs-coupling and cyclic AMP production without an exogenous ligand. Consequently, GPR3 deficient (GPR3KO) mice were more susceptible to developing experimental autoimmune uveitis (EAU) induced by immunization with interphotoreceptor retinoid-binding protein (IRBP) or by adoptive transfer of IRBP-specific T cells than their wild type (WT) littermates. T cells isolated from IRBP-immunized GPR3KO mice demonstrated an increase in proliferation and inflammatory cytokine production in response to the specific IRBP antigen and a relatively high resistance to activation-induced T cell death compared to T cells isolated from immunized WT mice. Moreover, a major tight junction protein such as ZO-1 was reduced in GPR3 deficient retina with severe uveitis after IRBP-specific T cells were transferred. Taken together, our findings suggest that constitutively active GPR3 inhibits T cell mediated retinal inflammation.
We discovered a protective role of G protein-coupled receptor 3 (GPR3) in a mouse model of T cell-mediated autoimmune uveitis. GPR3 is an orphan receptor that maintains Gs-coupling and cyclic AMP production without an exogenous ligand. Consequently, GPR3 deficient (GPR3KO) mice were more susceptible to developing experimental autoimmune uveitis (EAU) induced by immunization with interphotoreceptor retinoid-binding protein (IRBP) or by adoptive transfer of IRBP-specific T cells than their wild type (WT) littermates. T cells isolated from IRBP-immunized GPR3KO mice demonstrated an increase in proliferation and inflammatory cytokine production in response to the specific IRBP antigen and a relatively high resistance to activation-induced T cell death compared to T cells isolated from immunized WT mice. Moreover, a major tight junction protein such as ZO-1 was reduced in GPR3 deficient retina with severe uveitis after IRBP-specific T cells were transferred. Taken together, our findings suggest that constitutively active GPR3 inhibits T cell mediated retinal inflammation.
