Calnexin is necessary for T cell transmigration into the central nervous system

JCI Insight. 2018 Mar 8;3(5):e98410. doi: 10.1172/jci.insight.98410.


In multiple sclerosis (MS), a demyelinating inflammatory disease of the CNS, and its animal model (experimental autoimmune encephalomyelitis; EAE), circulating immune cells gain access to the CNS across the blood-brain barrier to cause inflammation, myelin destruction, and neuronal damage. Here, we discovered that calnexin, an ER chaperone, is highly abundant in human brain endothelial cells of MS patients. Conversely, mice lacking calnexin exhibited resistance to EAE induction, no evidence of immune cell infiltration into the CNS, and no induction of inflammation markers within the CNS. Furthermore, calnexin deficiency in mice did not alter the development or function of the immune system. Instead, the loss of calnexin led to a defect in brain endothelial cell function that resulted in reduced T cell trafficking across the blood-brain barrier. These findings identify calnexin in brain endothelial cells as a potentially novel target for developing strategies aimed at managing or preventing the pathogenic cascade that drives neuroinflammation and destruction of the myelin sheath in MS.

Keywords: Cell Biology; Chaperones; Multiple sclerosis; Neurological disorders; Neuroscience.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Blood-Brain Barrier / cytology
  • Blood-Brain Barrier / immunology*
  • Blood-Brain Barrier / pathology
  • Calnexin / genetics
  • Calnexin / immunology
  • Calnexin / metabolism*
  • Cell Movement / immunology
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Endothelial Cells / immunology
  • Endothelial Cells / pathology
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Mice
  • Mice, Transgenic
  • Middle Aged
  • Multiple Sclerosis / diagnostic imaging
  • Multiple Sclerosis / immunology*
  • Multiple Sclerosis / pathology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Up-Regulation
  • White Matter / diagnostic imaging
  • White Matter / immunology
  • White Matter / pathology


  • CANX protein, human
  • Canx protein, mouse
  • Calnexin