title: Role of DAF in protecting against T-cell autoreactivity that leads to experimental autoimmune uveitis.
abstract: OBJECTIVE
  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.
authors.affiliation: Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Fengqi
authors.initials: F
authors.lastname: An
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Zhidan
authors.initials: Z
authors.lastname: Tu
authors.forename: Hong
authors.initials: H
authors.lastname: Bu
authors.forename: Chi-Chao
authors.initials: CC
authors.lastname: Chan
authors.forename: Rachel R
authors.initials: RR
authors.lastname: Caspi
authors.forename: Feng
authors.initials: F
authors.lastname: Lin
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D015551:Autoimmunity / Q000502:physiology*; D018958:CD55 Antigens / Q000502:physiology*; D004195:Disease Models, Animal; D005136:Eye Proteins; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011994:Recombinant Proteins; D012177:Retinol-Binding Proteins; D018417:Th1 Cells / Q000276:immunology*; D015866:Uveitis, Posterior / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D000099214:Retinol-Binding Proteins, Interstitial
chemical_list: D018958:CD55 Antigens; D005136:Eye Proteins; D007371:Interferon-gamma; D020381:Interleukin-17; D011994:Recombinant Proteins; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial