Plasmacytoid Dendritic Cells Protect Against Atherosclerosis by Tuning T-Cell Proliferation and Activity

Isabelle T. M. N. Daissormont*, Anette Christ, Lieve Temmerman, Stefan Sampedro Millares, Torn Seijkens, Marco Manca, Mat Rousch, Marjorie Poggi, Louis Boon, Chris M. van der Loos, Mat J.A.P. Daemen, Esther Lutgens, Bente Halvorsen, Pal Aukrust, Edith M. Janssen, Erik A. L. Biessen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

98 Citations (Web of Science)

Abstract

Rationale: Unlike conventional dendritic cells, plasmacytoid DCs (PDC) are poor in antigen presentation and critical for type 1 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-gamma expression by splenic T cells, and plasma interferon-gamma 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. (Circ Res. 2011;109:1387-1395.)
Original languageEnglish
Pages (from-to)1387-1395
JournalCirculation Research
Volume109
Issue number12
DOIs
Publication statusPublished - 9 Dec 2011

Keywords

  • plasmacytoid dendritic cells
  • atherosclerosis
  • immune tolerance
  • T cells

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