Cutting Edge: TLR3 stimulation suppresses experimental autoimmune encephalomyelitis by inducing endogenous IFN-beta.
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-beta 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.
Touil
Tarik
T
Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Fitzgerald
Denise
D
Zhang
Guang-Xian
GX
Rostami
Abdolmohamad
A
Gran
Bruno
B
D000818:Animals; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D005434:Flow Cytometry; D007369:Interferon Inducers / Q000276:immunology / Q000494:pharmacology*; D016899:Interferon-beta / Q000096:biosynthesis / Q000187:drug effects* / Q000276:immunology; D053594:Myeloid Differentiation Factor 88 / Q000187:drug effects / Q000378:metabolism; D011070:Poly I-C / Q000276:immunology / Q000494:pharmacology*; D012330:RNA, Double-Stranded / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D051196:Toll-Like Receptor 3 / Q000819:agonists* / Q000187:drug effects / Q000276:immunology
D018932:Chemokine CCL2; D007369:Interferon Inducers; D053594:Myeloid Differentiation Factor 88; D012330:RNA, Double-Stranded; D051196:Toll-Like Receptor 3; D016899:Interferon-beta; D011070:Poly I-C