| First Author | An F | Year | 2009 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 50 |
| Issue | 8 | Pages | 3778-82 |
| PubMed ID | 19443714 | Mgi Jnum | J:154503 |
| Mgi Id | MGI:4368091 | Doi | 10.1167/iovs.08-3264 |
| Citation | An F, et al. (2009) Role of DAF in protecting against T-cell autoreactivity that leads to experimental autoimmune uveitis. Invest Ophthalmol Vis Sci 50(8):3778-82 |
| abstractText | PURPOSE: To investigate the role of decay-accelerating factor (DAF), a cell surface complement regulator that recently has been linked to T-cell responses and autoimmunity in the pathogenesis of experimental autoimmune uveitis (EAU). METHODS: EAU was induced in wild-type (WT) and Daf1(-/-) mice, and their disease severities, IRBP specific Th1/Th17 responses, and cytokine expression profiles were compared. In a test of the efficacy of treatment with soluble mouse DAF protein, EAU was induced in disease-susceptible B10.RIII mice, and they were treated with 0.5 mg soluble DAF protein or equal volume of PBS IP every other day. Retinal histology and IRBP-specific T-cell responses were compared after 14 days. RESULTS: Both EAU incidence and histopathology scores were significantly greater in Daf1(-/-) mice. There was a >10-fold greater mononuclear cell influx into the retina together with severe vasculitic lesions, retinal folding, and photoreceptor cell layer destruction. There were 5- to 7-fold greater Th1 and 3- to 4-fold greater Th17 responses against IRBP in Daf1(-/-) mice with EAU, and they expressed significantly elevated levels of GM-CSF, IL-2, IL-3, and IFN-gamma. WT B10.RIII mice that received soluble DAF protein treatments exhibited decreased IRBP-specific Th1/Th17 responses and were protected from retinal injury compared with the mice that received PBS treatments. CONCLUSIONS: DAF significantly influences IRBP-specific Th1 and Th17 responses and disease severity in EAU. Systemic upregulation of DAF levels could be used to suppress retinal antigen(s)-specific autoimmunity to treat autoimmune posterior uveitis. |
