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

Igal Ifergan, Hania Kébir, Monique Bernard, Karolina Wosik, Aurore Dodelet-Devillers, Romain Cayrol, Nathalie Arbour, Alexandre Prat*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

131 Scopus citations

Abstract

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-β and granulocyte-macrophage colony-stimulating factor. We also demonstrate that these dendritic cells secrete interleukin-12p70, transforming growth factor-β and interleukin-6 and promote the proliferation and expansion of distinct populations of interferon-γ- 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-β and granulocyte-macrophage colony-stimulating factor.

Original languageEnglish (US)
Pages (from-to)785-799
Number of pages15
JournalBrain
Volume131
Issue number3
DOIs
StatePublished - Mar 2008

Keywords

  • Blood-brain barrier
  • CNS
  • Dendritic cells
  • IL-17
  • Multiple sclerosis

ASJC Scopus subject areas

  • Clinical Neurology

Fingerprint Dive into the research topics of 'The blood-brain barrier induces differentiation of migrating monocytes into Th17-polarizing dendritic cells'. Together they form a unique fingerprint.

Cite this