Purchase this article with an account.
H. Shao, G. Jiang, Y. Ke, D. Sun, H. J. Kaplan; Activation of Retinal Astrocytes (RACs) Through TLR2 and NOD2 Enhances Uveitogenic T Cells. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4819.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To determine if MDP, a ligand for NOD2, has synergetic effects with the TLR ligands on RACs for activation of interphotoreceptor retinoid-binding protein (IRBP)-specific T cells.
The expression of NOD1 and 2 receptors on RACs of C57BL/6 mice was examined by real-time qPCR. The expression of MHC class II and costimulatory molecules and cytokine production by RACs before or after exposure to NLR and TLR ligands were assessed by flow cytometry and ELISA. The stimulatory effect of RACs on IRBP-specific T cells was examined by proliferation, cytokine production, and disease-inducing ability of activated IRBP-specific T cells. RACs derived from NOD2 deficient mice were also tested.
RACs constitutively express very low levels of both NOD1 and NOD2 mRNAs. MDP stimulation causes an increase in NOD2 mRNA. LPS and Poly I:C, ligands for TLR4 and TLR3 respectively, elicited a marked increase in NOD2 mRNA but not NOD1 mRNA. Expression of MHCII and CD86 molecules on RACs and production of IL-1β, TNF-α and IL-6 were up-regulated after exposure to MDP. Proliferation of IRBP-specific T cell was significantly increased after exposure to RACs pre-treated with BLP (for TLR2) and MDP. Furthermore, the activated T cells gained increased EAU-inducing activity compared to T cells exposed to RACs pre-treated with BLP or MDP alone. IRBP-specific T cells exposed to RACs derived from NOD2 knock out mice failed to express all of the above-mentioned features.
NOD2 and TLR2 ligands have a synergistic effect on the activation of RACs, leading to increased activation of IRBP-specific T cells. These results suggest that multiple microbial signals may affect susceptibility to autoimmune uveitis.
This PDF is available to Subscribers Only