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G. Jiang, D. Sun, Y. Ke, Y. Bian, H. J. Kaplan, H. Shao; The Functions of Retinal Astrocytes (RACs) to Re-Activate Auto-Reactive T Cells Is Regulated by TLR Ligations. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5143.
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© ARVO (1962-2015); The Authors (2016-present)
To determine the effect of TLR ligands on the activation of retinal astrocytes.
RACs were isolated from B6 mice, stimulated with different TLR ligands and assessed for their expression of MHC class II antigens and costimulatory molecules by flow cytometry. The ability of RACs after TLR stimulation to present antigens to interphotoreceptor retinoid-binding protein (IRBP)-specific T cells was examined by proliferation and cytokine-producing assays. RACs-activated IRBP-specific T cells were also tested for uveitogenic activity by adoptive transfer to naïve B6 recipients.
Cultured RACs expressed TLR2, TLR3, and TLR4, as tested by real time PCR and flow cytometry. Different TLR ligands have distinct stimulatory effect on astrocytes. LPS (TLR4 ligand) and poly I:C (TLR3 ligand) had greatest effect of stimulating astrocytes to acquire function of antigen-presentation, whereas BLP (TLR2 ligand) did not. Moreover, the effect of TLR ligand on RACs is dose dependent. IRBP T cells preferentially produced IFN-γ when exposed to the RACs pretreated with low dose of BLP (0.1 ug/ml), whereas predominantly produce IL-10 when exposed to RACs pre-treated with high dose (5 ug/ml) of BLP. IRBP1-20 specific T cells exposed to RACs pre-treated with LPS or poly I:C gained pathogenic activity, inducing EAU in naïve recipients, whereas those exposed to BLP did not.
RACs play an important regulatory role in re-activation of invading autoreactive T cells in the eye. The function of astrocytes is regulated by TLR ligands. Microbial antigen(s) provided by infectious agents may increase the susceptibility to autoimmune uveitis.
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