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Cell Metab. 2016 May 10;23(5):852-66. doi: 10.1016/j.cmet.2016.04.010.

Indoleamine 2,3-Dioxygenase-Expressing Aortic Plasmacytoid Dendritic Cells Protect against Atherosclerosis by Induction of Regulatory T Cells.

Author information

1
Laboratory of Cellular Physiology and Immunology, Institut de Recherches Cliniques de Montréal, Montréal, QC H2W 1R7, Canada; Division of Experimental Medicine, Department of Medicine, McGill University, Montréal, QC H3A 1A3, Canada.
2
Laboratory of Cellular Physiology and Immunology, Institut de Recherches Cliniques de Montréal, Montréal, QC H2W 1R7, Canada; Department of Microbiology, Infectiology, and Immunology, Université de Montréal, Montréal, QC H3C 3J7, Canada.
3
Department of Life Science, College of Natural Sciences, Research Institute for Natural Sciences, Hanyang University, Seoul 133-791, South Korea.
4
Department of Life Sciences, Ewha Womans University, Seoul 120-750, South Korea.
5
Laboratory Animal Resource Center, KRIBB, Chungbuk 363-883, South Korea.
6
Laboratory of Cellular Physiology and Immunology, Institut de Recherches Cliniques de Montréal, Montréal, QC H2W 1R7, Canada; Department of Molecular Biology, Université de Montréal, Montréal, QC H3C 3J7, Canada.
7
Laboratory of Human Retrovirology, Institut de Recherches Cliniques de Montréal, Montréal, QC H2W 1R7, Canada.
8
Institute for Immunology, Ludwig-Maximilians-Universität München, München 80336, Germany.
9
Department of Microbiology and Immunology, McGill University, Montréal, QC H3A 2B4, Canada.
10
Cardiovascular Center, and Department of Internal Medicine, Seoul National University Hospital, Seoul 110-744, South Korea.
11
Celldex Therapeutics, Hampton, NJ 08827, USA.
12
Centre de Santé et de Services Sociaux Jeanne-Mance, Montréal, QC H2H 2B4, Canada.
13
Department of Microbiology, Infectiology, and Immunology, Université de Montréal, Montréal, QC H3C 3J7, Canada; CHU Sainte-Justine Research Center, Montréal, QC H3T 1C5, Canada.
14
Department of Microbiology, Infectiology, and Immunology, Université de Montréal, Montréal, QC H3C 3J7, Canada; Laboratory of Human Retrovirology, Institut de Recherches Cliniques de Montréal, Montréal, QC H2W 1R7, Canada.
15
Research Center, Montréal Heart Institute, Montréal, QC H1T 1C8, Canada; Department of Pharmacology, Université de Montréal, Montréal, QC H3C 3J7, Canada.
16
Department of Cardiac Surgery, Montréal Heart Institute, Montréal, QC H1T 1C8, Canada.
17
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
18
Department of Life Sciences, Ewha Womans University, Seoul 120-750, South Korea. Electronic address: gootaeg@ewha.ac.kr.
19
Department of Life Science, College of Natural Sciences, Research Institute for Natural Sciences, Hanyang University, Seoul 133-791, South Korea. Electronic address: jchoi75@hanyang.ac.kr.
20
Laboratory of Cellular Physiology and Immunology, Institut de Recherches Cliniques de Montréal, Montréal, QC H2W 1R7, Canada; Division of Experimental Medicine, Department of Medicine, McGill University, Montréal, QC H3A 1A3, Canada; Department of Microbiology, Infectiology, and Immunology, Université de Montréal, Montréal, QC H3C 3J7, Canada. Electronic address: cheolho.cheong@ircm.qc.ca.

Abstract

Plasmacytoid dendritic cells (pDCs) are unique bone-marrow-derived cells that produce large amounts of type I interferon in response to microbial stimulation. Furthermore, pDCs also promote T cell tolerance in sterile-inflammation conditions. However, the immunomodulatory role of aortic pDCs in atherosclerosis has been poorly understood. Here, we identified functional mouse and human pDCs in the aortic intima and showed that selective, inducible pDC depletion in mice exacerbates atherosclerosis. Aortic pDCs expressed CCR9 and indoleamine 2,3-dioxygenase 1 (IDO-1), an enzyme involved in driving the generation of regulatory T cells (Tregs). As a consequence, loss of pDCs resulted in decreased numbers of Tregs and reduced IL-10 levels in the aorta. Moreover, antigen presentation by pDCs expanded antigen-specific Tregs in the atherosclerotic aorta. Notably, Tregs ablation affected pDC homeostasis in diseased aorta. Accordingly, pDCs in human atherosclerotic aortas colocalized with Tregs. Collectively, we identified a mechanism of atheroprotection mediated by tolerogenic aortic pDCs.

PMID:
27166946
DOI:
10.1016/j.cmet.2016.04.010
[Indexed for MEDLINE]
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