Plasmacytoid dendritic cells protect against atherosclerosis by tuning T-cell proliferation and activity

Circ Res. 2011 Dec 9;109(12):1387-95. doi: 10.1161/CIRCRESAHA.111.256529. Epub 2011 Oct 20.

Abstract

Rationale: Unlike conventional dendritic cells, plasmacytoid DCs (PDC) are poor in antigen presentation and critical for type I interferon response. Though proposed to be present in human atherosclerotic lesions, their role in atherosclerosis remains elusive.

Objective: To investigate the role of PDC in atherosclerosis.

Methods and results: We show that PDC are scarcely present in human atherosclerotic lesions and almost absent in mouse plaques. Surprisingly, PDC depletion by 120G8 mAb administration was seen to promote plaque T-cell accumulation and exacerbate lesion development and progression in LDLr⁻/⁻ mice. PDC depletion was accompanied by increased CD4⁺ T-cell proliferation, interferon-γ expression by splenic T cells, and plasma interferon-γ levels. Lymphoid tissue PDC from atherosclerotic mice showed increased indoleamine 2,3-dioxygenase (IDO) expression and IDO blockage abrogated the PDC suppressive effect on T-cell proliferation.

Conclusions: Our data reveal a protective role for PDC in atherosclerosis, possibly by dampening T-cell proliferation and activity in peripheral lymphoid tissue, rendering PDC an interesting target for future therapeutic interventions.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology*
  • Atherosclerosis / physiopathology*
  • CD4-Positive T-Lymphocytes / pathology*
  • Cell Proliferation*
  • Cells, Cultured
  • Coculture Techniques
  • Dendritic Cells / drug effects
  • Dendritic Cells / pathology*
  • Dendritic Cells / physiology*
  • Disease Models, Animal
  • Disease Progression
  • Female
  • Humans
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
  • Interferon-gamma / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, LDL / deficiency
  • Receptors, LDL / genetics
  • Receptors, LDL / metabolism

Substances

  • Antibodies, Monoclonal
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Receptors, LDL
  • Interferon-gamma