Regulation of autoimmune encephalomyelitis by toll-like receptors.
Experimental autoimmune encephalomyelitis (EAE) is a Th17-mediated autoimmune disease and an animal model for multiple sclerosis (MS). Complete Freund's adjuvant (CFA) contains pathogen-associated molecular patterns (PAMPs) that bind toll-like receptors (TLRs), and is necessary to induce EAE. Upstream TLR signals modify innate and adaptive immune responses in EAE. In detail, the common TLR adaptor molecule MyD88 is necessary for induction of EAE, and mediates activation of peripheral myeloid dendritic cells (mDCs) and differentiation of autoimmune Th17 cells. The stimulatory TLRs have not yet been identified for Th17 cells. TLR4 down regulates disease severity in EAE and Th17 cell responses, but promotes Th1 cell responses, which may inhibit the differentiation of Th17 cells. Moreover, treatment with a TLR4 ligand tolerizes mice and prevents EAE. TLR9 down regulates disease severity in myelin oligodendrocyte glycoprotein (MOG)-induced EAE, whereas it promotes disease in MOG(35-55)-induced EAE. Thus MyD88, TLR4 and TLR9 modify the disease process in EAE. Both endogenous and CFA-derived TLR ligands are implicated to modulate the disease process.
Marta
Monica
M
Neuroimmunology, Neuroscience Centre, ICMS, Barts and The London School of Medicine and Dentistry, London, UK. m.calado-marta@qmul.ac.uk
Meier
Ute C
UC
Lobell
Anna
A
D000818:Animals; D002454:Cell Differentiation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005620:Freund's Adjuvant; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors; D020381:Interleukin-17 / Q000276:immunology; D051379:Mice; D009103:Multiple Sclerosis / Q000276:immunology*; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000473:pathology; D051193:Toll-Like Receptors / Q000276:immunology*
D006023:Glycoproteins; D007155:Immunologic Factors; D020381:Interleukin-17; C571326:MOG protein, human; C571327:Mog protein, mouse; C507780:Myd88 protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D053594:Myeloid Differentiation Factor 88; D010446:Peptide Fragments; D051193:Toll-Like Receptors; C445081:myelin oligodendrocyte glycoprotein (35-55); D005620:Freund's Adjuvant