Work

Regulatory Role of TLR Ligands on the Activation of Autoreactive T Cells by Retinal Astrocytes

Year: 2009

Type: article

Abstract: PURPOSE: To determine whether Toll-like receptor (TLR) ligands regulate the activation of retinal astrocytes (RACs) and the possible role of RACs in the polarization of interphotoreceptor retinoid-binding protein (IRBP)-specific T cells. METHODS: TLR expression on RACs isolated from C57BL/6 mice was examined using real-time PCR and flow cytometry. The ability of RACs before or after treatment with TLR ligands to interact with T cells was assessed by measuring major histocompatibility complex class II and costimulatory molecule expression and cytokine production. The stimulatory effect of RACs, with or without TLR stimulation, on responder IRBP-specific T cells was examined by T-cell proliferation, cytokine production, and disease-inducing ability. RESULTS: Cultured mouse RACs expressed TLR2, TLR3, and TLR4. Different TLR ligands had distinct stimulatory effects on RACs. PolyI:C (a TLR3 ligand) had the greatest effect in stimulating RACs to acquire antigen-presentation function, whereas BLP (a TLR2 ligand) had the lowest effect. TLR3 ligation increased the expression of MHC and costimulatory molecules and induced the production of IL-6, IL-12, and IL-23 by RACs. IRBP-specific T cells activated by polyI:C-treated RACs expanded vigorously, produced significant amounts of IFN-gamma and IL-17, and induced experimental autoimmune uveitis when injected into naive mice. CONCLUSIONS: The stimulatory effect of RACs on autoreactive T cells is regulated by TLR ligands. TLR3 had a marked effect on the ability of RACs to promote the activation of Th1 and Th17 IRBP-specific T cells. Thus, exposure to microbial antigen(s) may alter susceptibility to autoimmune uveitis by promoting the activation of autoreactive T cells.

Source: Investigative Ophthalmology & Visual Science

DOI: 10.1167/iovs.08-3303

Authors: Guomin Jiang, Yan Ke, Deming Sun, Yali Wang, Henry J. Kaplan, Hui Shao

Institutions: University of Louisville, University of Southern California, Doheny Eye Institute

Language: English

Topic: Ocular Diseases and Behçet’s Syndrome

Subfield: Ophthalmology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funder: National Eye Institute