Inefficient clearance of myelin debris by microglia impairs remyelinating processes

J Exp Med. 2015 Apr 6;212(4):481-95. doi: 10.1084/jem.20141656. Epub 2015 Mar 16.


An imbalance between remyelinating and demyelinating rates underlies degenerative processes in demyelinating diseases such as multiple sclerosis. An optimal therapeutic strategy would be to stimulate remyelination while limiting demyelination. Although accumulation of myelin debris impairs remyelination, the mechanisms regulating the clearance of such debris by mononuclear phagocytic cells are poorly understood. We demonstrate that after cuprizone intoxication, CCR2-dependent infiltration of mouse bone marrow-derived cells is abundant in demyelinating areas, but that these cells do not impact demyelination. However, in CX3CR1-deficient mice, the clearance of myelin debris by microglia was blocked greatly, affecting the integrity of the axon and myelin sheaths and thus preventing proper remyelination. These results highlight the crucial role played by CX3CR1 in myelin removal and show that there can be no efficient remyelination after a primary demyelinating insult if myelin clearance by microglia is impaired.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / immunology*
  • Axons / pathology
  • Bone Marrow Cells / immunology*
  • Bone Marrow Cells / pathology
  • CX3C Chemokine Receptor 1
  • Demyelinating Diseases / genetics
  • Demyelinating Diseases / immunology*
  • Demyelinating Diseases / pathology
  • Mice
  • Mice, Knockout
  • Microglia / immunology*
  • Microglia / pathology
  • Myelin Sheath / immunology*
  • Myelin Sheath / pathology
  • Phagocytes / immunology*
  • Phagocytes / pathology
  • Receptors, CCR2 / genetics
  • Receptors, CCR2 / immunology
  • Receptors, Chemokine / genetics
  • Receptors, Chemokine / immunology


  • CX3C Chemokine Receptor 1
  • Ccr2 protein, mouse
  • Cx3cr1 protein, mouse
  • Receptors, CCR2
  • Receptors, Chemokine