The innate immune adaptor MyD88 is dispensable for spontaneous autoimmune demyelination in a mouse model of multiple sclerosis

Abstract Multiple sclerosis (MS) is an autoimmune disease that is mediated by myelin-reactive T cells resulting in CNS demyelination, however the mechanisms that control their activation are unclear. Mice that are transgenic for a myelin proteolipid protein (PLP)-specific TCR spontaneously develop e...

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Bibliographic Details
Published in:Journal of neuroimmunology 2013-02, Vol.255 (1), p.60-69
Main Authors: Wexler, Aaron G, Frielle, Christine, Berry, Gregory, Budgeon, Lynn R, Baccon, Jennifer, Christensen, Neil D, Waldner, Hanspeter
Format: Article
Language:English
Subjects:
adaptor proteins
Allergy and Immunology
Animal models
Animals
APCs
Autoimmune diseases
Cell activation
Central nervous system
Data processing
Demyelinating Diseases - genetics
Demyelinating Diseases - immunology
Demyelinating Diseases - metabolism
Demyelination
Dendritic cells
Disease Models, Animal
Encephalomyelitis, Autoimmune, Experimental - genetics
Encephalomyelitis, Autoimmune, Experimental - immunology
Encephalomyelitis, Autoimmune, Experimental - metabolism
Experimental allergic encephalomyelitis
Experimental autoimmune encephalomyelitis
Female
Helper cells
Immunity, Innate - genetics
Interleukin 1 receptors
Lymphocytes T
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Multiple sclerosis
Multiple Sclerosis - genetics
Multiple Sclerosis - immunology
Multiple Sclerosis - metabolism
MyD88
MyD88 protein
Myelin proteolipid protein
Myeloid Differentiation Factor 88 - deficiency
Myeloid Differentiation Factor 88 - genetics
Myeloid Differentiation Factor 88 - physiology
Neurology
Signal transduction
T cells
T-cell receptor
Transgenic mice
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Summary:Abstract Multiple sclerosis (MS) is an autoimmune disease that is mediated by myelin-reactive T cells resulting in CNS demyelination, however the mechanisms that control their activation are unclear. Mice that are transgenic for a myelin proteolipid protein (PLP)-specific TCR spontaneously develop experimental autoimmune encephalomyelitis (EAE), the animal model of MS. They mimic the spontaneous onset of MS and thus offer the unique opportunity to investigate the mechanisms that may contribute to the development of spontaneous CNS autoimmunity. MyD88 is an adaptor protein that mediates signal transduction by TLRs, IL-1R and IL-18R, resulting in the activation of innate immune cells, including DCs. We investigated the requirement of MyD88 in the pathogenesis of spontaneous EAE in PLP TCR transgenic SJL mice. We show that genetic loss of MyD88 does not intrinsically preclude development of spontaneous EAE and autoimmune demyelination in these mice. EAE was associated with functionally mature peripheral DCs that promoted superior PLP-specific Th1 and Th17 responses compared to those from disease-free mice. Together, our data suggest that MyD88-independent innate immune signaling critically contributes to priming of myelin-reactive T cells and development of spontaneous EAE in MyD88-deficient PLP TCR transgenic mice.
ISSN:0165-5728
1872-8421
DOI:10.1016/j.jneuroim.2012.11.004