Elevated expression of granulocyte-macrophage colony-stimulating factor receptor in multiple sclerosis lesions

J Neuroimmunol. 2018 Apr 15;317:45-54. doi: 10.1016/j.jneuroim.2017.12.017. Epub 2017 Dec 22.

Abstract

Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease that disproportionately affects young adults, leading to disability and high costs to society. Infiltration of T cells and monocytes into the central nervous system (CNS) is critical for disease initiation and progression. However, despite a great deal of effort the molecular mechanisms by which immune cells initiate and perpetuate CNS damage in MS have not yet been elucidated. In experimental autoimmune encephalomyelitis (EAE), an animal model of MS, granulocyte-macrophage colony-stimulating factor (GM-CSF) produced by pathogenic Th1 and Th17 cells is critical for the recruitment of monocytes into the CNS during the initial stage of disease. We and others have recently shown that, compared with healthy individuals, MS patients have greater numbers of CD4+ and CD8+ T cells that produce GM-CSF. Here, we describe the expression of GM-CSF and its receptor, GM-CSFR, in normal brain and MS lesions. Our data show that in acute and chronic MS lesions, microglia and astrocytes have upregulated expression of GM-CSFR; in addition, we show that GM-CSF-associated molecules are also upregulated in MS lesions. These findings further strengthen the argument that GM-CSF signaling contributes to MS pathogenesis.

Keywords: Astrocytes; GM-CSFR; Microglia; Multiple sclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged, 80 and over
  • Astrocytes / immunology
  • Astrocytes / metabolism*
  • Brain / immunology
  • Brain / metabolism*
  • Female
  • Humans
  • Male
  • Microglia / immunology
  • Microglia / metabolism*
  • Middle Aged
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / metabolism*
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis*
  • Up-Regulation

Substances

  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor