Novel Function of Extracellular Matrix Protein 1 in Suppressing Th17 Cell Development in Experimental Autoimmune Encephalomyelitis

J Immunol. 2016 Aug 15;197(4):1054-64. doi: 10.4049/jimmunol.1502457. Epub 2016 Jun 17.


Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS characterized by demyelination and axonal damage. Experimental autoimmune encephalomyelitis (EAE) is a well-established animal model for human MS. Although Th17 cells are important for disease induction, Th2 cells are inhibitory in this process. In this article, we report the effect of a Th2 cell product, extracellular matrix protein 1 (ECM1), on the differentiation of Th17 cells and the development of EAE. Our results demonstrated that ECM1 administration from day 1 to day 7 following the EAE induction could ameliorate the Th17 cell responses and EAE development in vivo. Further study of the mechanism revealed that ECM1 could interact with αv integrin on dendritic cells and block the αv integrin-mediated activation of latent TGF-β, resulting in an inhibition of Th17 cell differentiation at an early stage of EAE induction. Furthermore, overexpression of ECM1 in vivo significantly inhibited the Th17 cell response and EAE induction in ECM1 transgenic mice. Overall, our work has identified a novel function of ECM1 in inhibiting Th17 cell differentiation in the EAE model, suggesting that ECM1 may have the potential to be used in clinical applications for understanding the pathogenesis of MS and its diagnosis.

Publication types

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

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Extracellular Matrix Proteins / immunology*
  • Extracellular Matrix Proteins / pharmacology
  • Immunohistochemistry
  • Immunoprecipitation
  • Mass Spectrometry
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Real-Time Polymerase Chain Reaction
  • Th17 Cells / immunology*


  • Ecm1 protein, mouse
  • Extracellular Matrix Proteins