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

Aaron G. Wexler, Christine Frielle, Gregory Berry, Lynn R. Budgeon, Jennifer Baccon, Neil D. Christensen, Hanspeter Waldner

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)60-69
Number of pages10
JournalJournal of Neuroimmunology
Volume255
Issue number1-2
DOIs
StatePublished - Feb 15 2013
Externally publishedYes

Fingerprint

Autoimmune Experimental Encephalomyelitis
Demyelinating Diseases
Multiple Sclerosis
Proteolipids
Transgenic Mice
Myelin Sheath
Proteins
Myelin Proteolipid Protein
T-Lymphocytes
Autoimmunity
Autoimmune Diseases
Signal Transduction
Animal Models

Keywords

  • APCs
  • Experimental autoimmune encephalomyelitis
  • MyD88
  • T cells

ASJC Scopus subject areas

  • Immunology
  • Clinical Neurology
  • Immunology and Allergy
  • Neurology

Cite this

The innate immune adaptor MyD88 is dispensable for spontaneous autoimmune demyelination in a mouse model of multiple sclerosis. / Wexler, Aaron G.; Frielle, Christine; Berry, Gregory; Budgeon, Lynn R.; Baccon, Jennifer; Christensen, Neil D.; Waldner, Hanspeter.

In: Journal of Neuroimmunology, Vol. 255, No. 1-2, 15.02.2013, p. 60-69.

Research output: Contribution to journalArticle

Wexler, Aaron G. ; Frielle, Christine ; Berry, Gregory ; Budgeon, Lynn R. ; Baccon, Jennifer ; Christensen, Neil D. ; Waldner, Hanspeter. / The innate immune adaptor MyD88 is dispensable for spontaneous autoimmune demyelination in a mouse model of multiple sclerosis. In: Journal of Neuroimmunology. 2013 ; Vol. 255, No. 1-2. pp. 60-69.
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