title: The role of TLR2, TRL3, TRL4, and TRL9 signaling in the pathogenesis of autoimmune disease in a retinal autoimmunity model.
abstract: OBJECTIVE
  Induction of tissue-specific experimental autoimmune diseases involves the use of complete Freund adjuvant containing Mycobacterium tuberculosis, whose recognition by the innate immune system depends on Toll-like receptors (TLRs) that signal through the adaptor molecule MyD88. The authors' previous study showed that MyD88(-/-) mice, but not TLR2(-/-), TLR4(-/-), or TLR9(-/-) mice, were resistant to experimental autoimmune uveitis (EAU).
  
  
  METHODS
  The EAU induction in mice deficient in TLR3 or mice double deficient in TLR2+4, TLR2+9, and TLR4+9 was examined and the role of the TLR agonists in the adjuvant effect involved in the induction of EAU was assessed.
  
  
  RESULTS
  TLR3-deficient and TLR2+4, TLR2+9, and TLR4+9 double-deficient mice were as susceptible to EAU as their control littermates. However, in mice immunized with a low-dose EAU regimen, TLR4 agonist lipopolysaccharide (LPS) enhanced EAU scores, delayed-type hypersensitivity responses, and antigen-specific T-cell proliferation. Antigen-specific IL-17 and IFN-gamma production by T lymphocytes was markedly increased in the LPS-treated group. The effects of LPS on EAU were abolished by treatment with an LPS deactivator polymyxin B. Inclusion of agonists for TLR2, TRL3, or TRL9 in immunization also enhanced EAU scores.
  
  
  CONCLUSIONS
  These results suggest that signaling of TLR2, TRL3, TRL4, and TRL9 is highly redundant in the adjuvant effect needed to induce EAU and that diverse microbial infections may contribute to the pathogenesis of diseases such as uveitis.
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jiazhu
authors.initials: J
authors.lastname: Fang
authors.forename: Dan
authors.initials: D
authors.lastname: Fang
authors.forename: Phyllis B
authors.initials: PB
authors.lastname: Silver
authors.forename: Feng
authors.initials: F
authors.lastname: Wen
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Ren
authors.forename: Qing
authors.initials: Q
authors.lastname: Lin
authors.forename: Rachel R
authors.initials: RR
authors.lastname: Caspi
authors.forename: Shao Bo
authors.initials: SB
authors.lastname: Su
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000276:immunology; D005260:Female; D020868:Gene Silencing / Q000502:physiology; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000502:physiology*; D012177:Retinol-Binding Proteins / Q000276:immunology; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000502:physiology; D051196:Toll-Like Receptor 3 / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000502:physiology; D051217:Toll-Like Receptor 9 / Q000502:physiology; D051193:Toll-Like Receptors / Q000819:agonists / Q000502:physiology*; D014605:Uveitis / Q000276:immunology*; D000099214:Retinol-Binding Proteins, Interstitial
chemical_list: D001324:Autoantigens; D005136:Eye Proteins; D007371:Interferon-gamma; D020381:Interleukin-17; D008070:Lipopolysaccharides; D053594:Myeloid Differentiation Factor 88; D012177:Retinol-Binding Proteins; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors; D000099214:Retinol-Binding Proteins, Interstitial; C519703:TLR3 protein, mouse; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; C495370:Tlr9 protein, mouse