Vessel wall-embedded dendritic cells induce T-cell autoreactivity and initiate vascular inflammation

Ji W. Han, Kazunori Shimada, Wei Ma-Krupa, Tiffany L. Johnson, Robert M. Nerem, Jörg J. Goronzy, Cornelia M. Weyand

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

Human medium-sized and large arteries are targeted by inflammation with innate and adaptive immune responses occurring within the unique microspace of the vessel wall. How 3D spatial arrangements influence immune recognition and cellular response thresholds and which cell populations sense immunoactivating ligands and function as antigen-presenting cells are incompletely understood. To mimic the 3D context of human arteries, bioartificial arteries were engineered from collagen type I matrix, human vascular smooth muscle cells (VSMCs), and human endothelial cells and populated with cells implicated in antigen presentation and T-cell stimulation, including monocytes, macrophages, and myeloid dendritic cells (DCs). Responsiveness of wall-embedded antigen-presenting cells was probed with the Toll-like receptor ligand lipopolysaccharide, and inflammation was initiated by adding autologous CD4 T cells. DCs colonized the outermost VSMC layer, recapitulating their positioning at the media-adventitia border of normal arteries. Wall-embedded DCs responded to the microbial product lipopolysaccharide by entering the maturation program and upregulating the costimulatory ligand CD86. Activated DCs effectively stimulated autologous CD4 T cells, which produced the proinflammatory cytokine interferon-γ and infiltrated deeply into the VSMC layer, causing matrix damage. Lipopolysaccharide-triggered macrophages were significantly less efficacious in recruiting T cells and promoting T-cell stimulation. CD14 monocytes, even when preactivated, failed to support initial steps of vascular wall inflammation. Innate immune cells, including monocytes, macrophages, and DCs, display differential functions in the vessel wall. DCs are superior in sensing pathogen-derived motifs and are highly efficient in breaking T-cell tolerance, guiding T cells toward proinflammatory and tissue-invasive behavior.

Original languageEnglish (US)
Pages (from-to)546-553
Number of pages8
JournalCirculation research
Volume102
Issue number5
DOIs
StatePublished - Mar 2008

Keywords

  • Arteries
  • Bioengineered vessel
  • Dendritic cells
  • Immune system
  • Inflammation
  • Interleukins
  • Toll-like receptors

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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