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Cutting Edge: TLR3 Stimulation Suppresses Experimental Autoimmune Encephalomyelitis by Inducing Endogenous IFN-¹

Tarik Touil^*, Denise Fitzgerald^*, Guang-Xian Zhang^*, Abdolmohamad Rostami^* and Bruno Gran^2,*,

^* Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107; and Division of Clinical Neurology, University of Nottingham, Nottingham, United Kingdom

Experimental autoimmune encephalomyelitis is a well-characterized model of cell-mediated autoimmunity. TLRs expressed on APCs recognize microbial components and induce innate immune responses, leading to the elimination of invading infectious agents. Certain TLR agonists have been reported to have adjuvant properties in CNS autoimmune inflammatory demyelination. We report in this study that TLR3 stimulation by polyinosinic-polycytidylic acid, a double-stranded RNA analog, suppresses relapsing demyelination in a murine experimental autoimmune encephalomyelitis model. Disease suppression is associated with the induction of endogenous IFN- and the peripheral induction of the CC chemokine CCL2. These data indicate that a preferential activation of the MyD88-independent, type I IFN-inducing TLR pathway has immunoregulatory potential in this organ-specific autoimmune disease.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by grants from the National Institutes of Health (to A.R.), the National Multiple Sclerosis Society (to B.G. and A.R.), and the Mary E. Groff Surgical Medical Research and Education Charitable Trust (to B.G.).

² Address correspondence and reprint requests to Dr. Bruno Gran, Division of Clinical Neurology, University of Nottingham; B31 Medical School, Queen’s Medical Centre, Nottingham NG7 2UH, United Kingdom. E-mail address: bruno.gran{at}nottingham.ac.uk

³ Abbreviations used in this paper: EAE, experimental autoimmune encephalomyelitis; BMDC, bone marrow dendritic cell; IRF, IFN regulatory factor; LFB, Luxol fast blue; Mal, MyD88 adaptor-like protein; MS, multiple sclerosis; p.i., postimmunization; PLP, proteolipid protein; poly I:C, polyinosinic-polycytidylic acid; TRIF, Toll/IL-1R domain-containing adaptor protein inducing IFN-.

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