The blood-brain barrier induces differentiation of migrating monocytes into Th17-polarizing dendritic cells

Brain. 2008 Mar;131(Pt 3):785-99. doi: 10.1093/brain/awm295. Epub 2007 Dec 20.


Trafficking of antigen-presenting cells into the CNS is essential for lymphocyte reactivation within the CNS compartment. Although perivascular dendritic cells found in inflammatory lesions are reported to polarize naive CD4+ T lymphocytes into interleukin-17-secreting-cells, the origin of those antigen-presenting cells remains controversial. We demonstrate that a subset of CD14+ monocytes migrate across the inflamed human blood-brain barrier (BBB) and differentiate into CD83+CD209+ dendritic cells under the influence of BBB-secreted transforming growth factor-beta and granulocyte-macrophage colony-stimulating factor. We also demonstrate that these dendritic cells secrete interleukin-12p70, transforming growth factor-beta and interleukin-6 and promote the proliferation and expansion of distinct populations of interferon-gamma-secreting Th1 and interleukin-17-secreting Th17 CD4+ T lymphocytes. We further confirmed the abundance of such dendritic cells in situ, closely associated with microvascular BBB-endothelial cells within acute multiple sclerosis lesions, as well as a significant number of CD4+ interleukin-17+ T lymphocytes in the perivascular infiltrate. Our data support the notion that functional perivascular myeloid CNS dendritic cells arise as a consequence of migration of CD14+ monocytes across the human BBB, through the concerted actions of BBB-secreted transforming growth factor-beta and granulocyte-macrophage colony-stimulating factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigen Presentation / immunology
  • Blood-Brain Barrier / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Differentiation* / immunology
  • Cell Movement / immunology
  • Cells, Cultured
  • Chemokines / biosynthesis
  • Dendritic Cells / immunology*
  • Endothelium / immunology
  • Humans
  • Interferon-gamma / immunology
  • Interleukin-17 / biosynthesis
  • Lipopolysaccharide Receptors / analysis
  • Lymphocyte Culture Test, Mixed
  • Middle Aged
  • Monocytes / cytology
  • Monocytes / immunology*
  • Multiple Sclerosis / immunology*
  • Phagocytosis / immunology
  • Phenotype
  • Tumor Necrosis Factor-alpha / immunology


  • Chemokines
  • Interleukin-17
  • Lipopolysaccharide Receptors
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma