Toll-like receptor 3 ligand polyinosinic:polycytidylic acid enhances autoimmune disease in a retinal autoimmunity model

Abstract: Viral components can trigger autoimmunity, but the involved mechanisms remain to be elucidated. Toll-like receptor 3 (TLR3) recognizes viral double-stranded RNA (dsRNA) and appears to play an important role in this context. Our previous studies showed that signaling of TLR2, TLR3, TLR4 and TLR9 is highly redundant in the adjuvant effect needed to induce experimental autoimmune uveitis (EAU), an animal model of human autoimmune eye disease. In this study, we analyzed the effects of systemic delivery of polyinosinic:polycytidylic acid (poly(I:C)), a mimic of viral dsRNA, in the induction of EAU. We found that TLR3 agonist poly(I:C) enhanced EAU scores, DTH responses and Ag-specific T cell proliferation. In addition, Ag-specific Interleukin 17 (IL-17) and interferon gamma (IFN-γ) production by draining lymph node cells was markedly increased in the poly(I:C)-treated group. Our results suggest that activation of innate immune system mediated by TLR3 signaling pathway is of importance in the pathogenesis of virus-induced autoimmune diseases. [Copyright &y& Elsevier]