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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 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.
AuthorsAaron G Wexler, Christine Frielle, Gregory Berry, Lynn R Budgeon, Jennifer Baccon, Neil D Christensen, Hanspeter Waldner
JournalJournal of neuroimmunology (J Neuroimmunol) Vol. 255 Issue 1-2 Pg. 60-9 (Feb 15 2013) ISSN: 1872-8421 [Electronic] Netherlands
PMID23269203 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 Elsevier B.V. All rights reserved.
Chemical References
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
Topics
  • Animals
  • Demyelinating Diseases (genetics, immunology, metabolism)
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental (genetics, immunology, metabolism)
  • Female
  • Immunity, Innate (genetics)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Multiple Sclerosis (genetics, immunology, metabolism)
  • Myeloid Differentiation Factor 88 (deficiency, genetics, physiology)

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