The role of TLR2, TRL3, TRL4, and TRL9 signaling in the pathogenesis of autoimmune disease in a retinal autoimmunity model

Jiazhu Fang, Phyllis B. Silver, Dan Fang, Feng Wen, Bing Li, Xiangrong Ren, Rachel R. Caspi, Shao Bo Su

Research output: Contribution to journalArticlepeer-review

56 Scopus citations


Purpose. 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-y 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.

Original languageEnglish (US)
Pages (from-to)3092-3099
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Issue number6
StatePublished - Jun 2010
Externally publishedYes

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience


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