We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
The blood-brain barrier induces differentiation of migrating monocytes into Th17-polarizing dendritic cells.
- Authors
Igal Ifergan; Hania Kébir; Monique Bernard; Karolina Wosik; Aurore Dodelet-Devillers; Romain Cayrol; Nathalie Arbour; Alexandre Prat
- 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.
- Publication
Brain: A Journal of Neurology, 2008, Vol 131, Issue 3, p785
- ISSN
0006-8950
- Publication type
Academic Journal
- DOI
10.1093/brain/awm295