Altered Levels of Toll-Like Receptors in Circulating Extracellular Vesicles in Multiple Sclerosis

Cells. 2019 Sep 10;8(9):1058. doi: 10.3390/cells8091058.

Abstract

Extracellular vesicles (EVs) are involved in inter-cellular communication and their cargo may provide prognostic/diagnostic biomarkers. To discover EV-associated biomarkers for Multiple Sclerosis (MS), we used an immune marker array to identify surface proteins on circulating EVs that differ between MS patients and controls (n = 3 each). We identified toll-like receptor-3 (TLR3) as a potential target for further validation. We utilized prospectively collected serum from relapsing-remitting MS patients (n = 18) and controls (n = 16) and confirmed lower concentration of TLR3 and higher concentration of mechanistically related TLR4 in MS EVs compared to controls. Future studies may further evaluate the utility of EV-associated TLRs as MS biomarkers and uncover their mechanistic significance.

Keywords: TLR3; TLR4; extracellular vesicles; innate immunity; multiple sclerosis.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood
  • Cell Communication
  • Extracellular Vesicles / metabolism
  • Extracellular Vesicles / physiology*
  • Female
  • Humans
  • Immunity, Innate / immunology
  • Immunity, Innate / physiology
  • Male
  • Membrane Proteins / metabolism
  • Middle Aged
  • Multiple Sclerosis / metabolism*
  • Multiple Sclerosis / physiopathology
  • Multiple Sclerosis, Relapsing-Remitting / metabolism
  • Prognosis
  • Toll-Like Receptor 3 / analysis
  • Toll-Like Receptor 3 / metabolism
  • Toll-Like Receptor 4 / analysis
  • Toll-Like Receptor 4 / metabolism
  • Toll-Like Receptors / metabolism*
  • Toll-Like Receptors / physiology

Substances

  • Biomarkers
  • Membrane Proteins
  • TLR3 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 3
  • Toll-Like Receptor 4
  • Toll-Like Receptors