Fatal demyelinating disease is induced by monocyte-derived macrophages in the absence of TGF-β signaling

Nat Immunol. 2018 May;19(5):1-7. doi: 10.1038/s41590-018-0091-5. Epub 2018 Apr 16.


The cytokine transforming growth factor-β (TGF-β) regulates the development and homeostasis of several tissue-resident macrophage populations, including microglia. TGF-β is not critical for microglia survival but is required for the maintenance of the microglia-specific homeostatic gene signature1,2. Under defined host conditions, circulating monocytes can compete for the microglial niche and give rise to long-lived monocyte-derived macrophages residing in the central nervous system (CNS)3-5. Whether monocytes require TGF-β for colonization of the microglial niche and maintenance of CNS integrity is unknown. We found that abrogation of TGF-β signaling in CX3CR1+ monocyte-derived macrophages led to rapid onset of a progressive and fatal demyelinating motor disease characterized by myelin-laden giant macrophages throughout the spinal cord. Tgfbr2-deficient macrophages were characterized by high expression of genes encoding proteins involved in antigen presentation, inflammation and phagocytosis. TGF-β is thus crucial for the functional integration of monocytes into the CNS microenvironment.

Publication types

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

MeSH terms

  • Animals
  • Brain / immunology*
  • Brain / metabolism
  • Brain / pathology
  • Demyelinating Diseases / immunology*
  • Demyelinating Diseases / metabolism
  • Demyelinating Diseases / pathology
  • Macrophages / immunology
  • Macrophages / metabolism
  • Macrophages / pathology*
  • Mice
  • Signal Transduction
  • Spinal Cord / immunology*
  • Spinal Cord / metabolism
  • Spinal Cord / pathology
  • Transforming Growth Factor beta / immunology*
  • Transforming Growth Factor beta / metabolism


  • Transforming Growth Factor beta